Paternal thrombophilia and recurrent implantation failure: an exploratory case-control study.

OBJECTIVE: Many pieces of literature have reported that inherited and acquired thrombophilia might be a risk factor for recurrent implantation failure (RIF), however, most studies have only focused on RIF patients and not their male partners. We studied the possible association of paternal thrombophilia with RIF risk. METHODS: Forty-two male partners aged 20-45 suffered from RIF compared with 42 males from couples with at least one successful pregnancy. All participants were investigated for thrombophilia markers. RESULTS: The prevalence of coagulation Factor V activity was significantly higher in the case group (42.9%) than in the control group (16.7%) (p=0.008) (OR=3.75; 95% CI, 1.38, 10.12). The prevalence of protein C and protein S deficiencies in RIF patients were 4.8% and 2.4%, respectively, and 0% in the controls. The prevalence of antithrombin III (ATIII) deficiency was significantly higher in the case group (19%) than in the control group (2.4%) (p=0.01). None of MTHFR C677T and MTHFR A1298C were statistically significant between the two groups. Combined thrombophilia was 45.2% in the men of the RIF group when compared with the control, 14.2% (p=0.001) (OR = 4.95; 95% CI, 1.75-13.86). CONCLUSIONS: Paternal thrombophilia may be related to recurrent implantation failure, so evaluation of this factor in RIF patients could be used to identify relevant risk groups and may help in the proper management of these cases to enhance the chance of implantation.

Effect of nifedipine administration before embryo transfer on reproductive outcome in ICSI cycles, a double-blind control trial study.

PURPOSE: Nifedipine is a calcium channel blocker with smooth muscle relaxing properties. This study set out to investigate the efficacy of nifedipine administered orally before embryo transfer (ET) on the improvement of the intracytoplasmic sperm injection (ICSI) outcome. This randomized, double-blind, comparator-controlled, was carried out between 2019 and 2020 in the infertility center of Babol, Iran. 200 women candidates for ICSI and recipients of frozen-thawed ET aged 18-40 years were randomly assigned in the ratio 1:1 to an intervention group that received nifedipine 20 mg tablets orally 30 min before ET (n = 100) or to a group of placebo (n = 100). A randomization center in Babol University of Medical Science used computer-generated numbers to allocate treatments. The allocation treatment was blind to the participants, the sonographer of endometer monitoring, the staff of the ICSI laboratory, and the outcome assessor. The primary analysis was based on the intention-to-treat principle done on 200 participants, (n = 100), comparing chemical pregnancy rates in the two comparing groups at 14 days' follow-up after ET. Implantation rate and clinical pregnancy were considered secondary outcomes. RESULT: 200 participants were analyzed. There is no significant difference in the number of oocytes and the quality of embryos in the nifedipine and placebo groups. Despite a numerical increase in the rate of chemical pregnancy, there were no statistical differences in the study group versus the comparison group (24% vs 14%, P = 0.1, rate ratio 0.88, 95% CI 0.77 to 1.01), respectively. Also, no significant increase in clinical pregnancy was found compared with the placebo (17% vs 8%, P = 0.26, rate ratio 0.90, 0.81 to 1.00). CONCLUSION: Nifedipine administered orally 30 min before embryo transfer did not improve the chemical pregnancy rate, and clinical pregnancy rate in infertile women undergoing ICSI. This trial has been registered on the Iranian Clinical Trials Registration Site (IRCT) with the number IRCT20180417039338N3.

Polychlorinated biphenyls and the risk of endometriosis: Systematic review and meta-analysis.

OBJECTIVE: We aimed to collect recent findings for a deeper understanding of the association between human exposure to polychlorinated biphenyls (PCBs) and endometriosis development. METHODS: Web of Science, PubMed, Scopus, Google Scholar, and Embase were searched based on inclusion criteria from 2000 to the end of 2020. No filter was exerted to limit the language of publications and geographical restriction. Odds ratios (OR) using the random-effects model and the corresponding 95% confidence interval (CI) were calculated for each included study. RESULTS: Fourteen studies were included in our analyses. The pooled OR and 95% CI for PCB was 1.96 (1.31 to 2.93). Despite being statistically significant, there was evidence of moderate heterogeneity (I2 = 63%, P = 0.001, τ2 = 0.32). Findings from our subgroup analyses showed a significant association between PCB exposure and endometriosis among European population (OR = 3.66, 95% CI: 2.08-6.44). Also a positive association was detected between PCB exposure and an increased odds of endometriosis in studies with laparoscopy (OR = 2.32, 95% CI: 1.16-4.63) or surgery confirm of controls (OR = 1.39, 95% CI: 1.02-1.89). Moreover, according to matched-pairs design, a significant association between PCB exposure and endometriosis development was detected (OR = 1.51, 95% CI: 1.04-2.18), also heterogeneity decreased in studies with matched-pairs design (I2 = 30.4%). CONCLUSIONS: Findings of this study confirm an association between endometriosis and exposure to PCB. However, more primary studies using proper methodology are needed to confirm this association.

Combined Parental Thrombophilia Gene Mutation Defects in Couples with Repeated Pregnancy Loss.

Background: Several genetic mutations in female thrombotic defects have recently been shown to affect recurrent pregnancy loss (RPL); however, it is unclear which common parental mutations are involved in thrombosis-associated repeated pregnancy loss RPL. Aims: In this study, the prevalence of some combined parental thrombophilia gene mutation defects was studied in couples with RPL. Settings and Design: The observational study was done in babol infertility research center (Iran) in 2022. Materials and Methods: Sixty-two infertile women with a history of RPL and their male partners (124 individuals) participated in this study. The frequencies of common defects associated with methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, factor V Leiden, protein C, protein S and homocysteine were analysed in these couples. Statistical analysis used: The data were statistically analysed using the Mann-Whitney test. Results: Sixty-two couples (124 individuals) were analysed. 56.2% of couples with a history of RPL had MTHFR C677T and 23.1% had MTHFR A1298C. Forty percent of couples showed homocysteine deficiency and 12.5% protein C deficiency. Other genes tested were only observed in the mother or father but not both. Conclusions: Results obtained with RPL couples demonstrate the importance of further investigating combined parental thrombophilia gene mutation defects (not only maternal).

Developing machine learning-based models to predict intrauterine insemination (IUI) success by address modeling challenges in imbalanced data and providing modification solutions for them.

BACKGROUND: This study sought to provide machine learning-based classification models to predict the success of intrauterine insemination (IUI) therapy. Additionally, we sought to illustrate the effect of models fitting with balanced data vs original data with imbalanced data labels using two different types of resampling methods. Finally, we fit models with all features against optimized feature sets using various feature selection techniques. METHODS: The data for the cross-sectional study were collected from 546 infertile couples with IUI at the Fatemehzahra Infertility Research Center, Babol, North of Iran. Logistic regression (LR), support vector classification, random forest, Extreme Gradient Boosting (XGBoost) and, Stacking generalization (Stack) as the machine learning classifiers were used to predict IUI success by Python v3.7. We employed the Smote-Tomek (Stomek) and Smote-ENN (SENN) resampling methods to address the imbalance problem in the original dataset. Furthermore, to increase the performance of the models, mutual information classification (MIC-FS), genetic algorithm (GA-FS), and random forest (RF-FS) were used to select the ideal feature sets for model development. RESULTS: In this study, 28% of patients undergoing IUI treatment obtained a successful pregnancy. Also, the average age of women and men was 24.98 and 29.85 years, respectively. The calibration plot in this study for IUI success prediction by machine learning models showed that between feature selection methods, the RF-FS, and among the datasets used to fit the models, the balanced dataset with the Stomek method had well-calibrating predictions than other methods. Finally, the brier scores for the LR, SVC, RF, XGBoost, and Stack models that were fitted utilizing the Stomek dataset and the chosen feature set using the Random Forest technique obtained equal to 0.202, 0.183, 0.158, 0.129, and 0.134, respectively. It showed duration of infertility, male and female age, sperm concentration, and sperm motility grading score as the most predictable factors in IUI success. CONCLUSION: The results of this study with the XGBoost prediction model can be used to foretell the individual success of IUI for each couple before initiating therapy.

Human Exposure to Polychlorinated Biphenyls (PCBs) and The Risk of Endometriosis: A Systematic Review and Meta-Analysis Protocol.

Endometriosis is one of the gynecological disorders and its prevalence is estimated to 8.10% of reproductive-age women. In Iran, the frequency of endometriosis was reported at 29% among infertile women. The etiology of endometriosis is still unclear. Numerous environmental contaminants such as polychlorinated biphenyls (PCBs) may play important roles in endometriosis development and etiology. Iranian population has relatively low levels of PCBs. However, no studies have evaluated PCBs levels in Iranian endometriosis patients so far. At present, there is no systematic review of the relationship between only PCBs exposure and the risk of endometriosis. The aim of this systematic review and meta-analysis protocol will be to evaluate the association between only PCBs exposure and the risk of endometriosis. PubMed/MEDLINE, Web of Science, Scopus, Google Scholar, Embase, key journals, conferences/congress research papers, and the references of included primary studies will be searched. Observational studies (cross-sectional, case-control, and cohort) in humans that investigated the association between PCBs exposure and the risk of endometriosis will be included. The outcome will be endometriosis risk in association with PCBs exposure. The primary screening and data extraction will be performed by three team members independently and will be judged by opinion with the fourth member. The modified Newcastle-Ottawa Scale (NOS) will be used for the quality assessment of studies. Findings from this study will recognize the association between PCBs exposure and the risk of endometriosis. Results may provide a new window for identifying the role of PCBs as environmental risk factors in relation to the development of endometriosis. Registration number: PROSPERO; CRD42019120539.

Using autologous intrauterine platelet-rich plasma to improve the reproductive outcomes of women with recurrent implantation failure.

OBJECTIVE: Reproductive clinics are often faced with cases of repeated implantation failure (RIF). This study evaluated whether platelet-rich plasma (PRP) might improve the implantation outcomes of patients suffering from RIF. METHODS: Thirty women with RIF submitted to frozen-thawed embryo transfers were included in the study. Intrauterine infusions of autologous purified platelet preparations were administered 48 hours prior to embryo transfer. Differences in implantation, clinical pregnancy, and miscarriage rates of cycles with and without PRP infusions were analyzed. RESULTS: The implantation rate seen in the PRP group was 6.7%. No significant difference was found the between the implantation, clinical pregnancy, ongoing pregnancy, and miscarriage rates of frozen-thawed embryo transfers with and without PRP infusion. However, the effect size of PRP infusion (Cohen's d=0.39) on implantation rates revealed a relationship in medium strength. CONCLUSION: Platelet-rich plasma might potentially yield beneficial effects as a safe therapeutic option offered alongside other treatments designed to improve the reproductive outcomes of women with repeated implantation failure.

Factors associated with spontaneous abortion following intracytoplasmic sperm injection (ICSI).

OBJECTIVE: The aim of this study was to describe the miscarriage rates and the factors associated with cases of spontaneous abortion observed in women offered intracytoplasmic sperm injection (ICSI). METHODS: This cross-sectional study enrolled women who became pregnant with the aid of ICSI treated at the Babol Infertility Center (Iran) within a period of five years (2010-2015). Data were collected from patient charts and, in some cases, through phone calls. The study looked into the incidence of spontaneous abortion in women offered ICSI and the factors associated with miscarriage. The chi-square test, Fisher's exact test, and the t-test were used to analyze the data. RESULTS: From a total of 145 pregnant women, 120 were included in our study. The prevalence of miscarriage was 20%. Galactorrhea was significantly more present in patients who had miscarriages (25% vs. 9.37%, p=0.04). There was a marked difference in the duration of infertility of miscarriage and non-miscarriage patients offered ICSI (6.6±8.3 vs. 4.9±7.3 years, p=0.05). No association was found between maternal age, BMI, cause of infertility, hormonal pattern, type of infertility, history of surgery, polycystic ovary syndrome, number of oocytes, or day of retrieval with miscarriage.

Prolactin concentration in various stages of endometriosis in infertile women.

OBJECTIVE: The relation between excessive prolactin and endometriosis-related infertility is debatable. Anovulation or defective luteal phase occurs frequently due to hyperprolactinemia in subfertile women. In this investigation, we evaluated the association between serum prolactin levels and the severity of endometriosis. METHODS: This retrospective cohort study carried out at the Babol Infertility Research Center looked into the baseline serum prolactin levels of 114 infertile women with endometriosis and compared them to the levels seen in 101 infertile women without endometriosis (controls). Statistical analysis included independent t-test, chi-square, Welch test and ROC curve analysis. RESULTS: Infertile women with endometriosis had significantly higher serum prolactin levels than infertile women without endometriosis (p=0.003). A significant difference was detected between controls and individuals with endometriosis stages III/IV (p-value=0.009). Prolactin was found to have diagnostic value to detect endometriosis stages III/IV vs. stages I/II in AUC=0.65, 95% CI (0.55, 0.76). Prolactin values with a cut off set at 20.08 ng/mL had a sensitivity of 0.74 and specificity of 0.54 in detecting disease stages III/IV vs. I/II. The prognostic capability of prolactin in detecting endometriosis in cases vs. controls by ROC curve analysis had an AUC=+0.67, 95% CI (0.60, 0.74). Prolactin values with a cut off set at 17.5 ng/mL had a sensitivity of 0.64 and specificity of 0.63 in segregating subjects with and without endometriosis. CONCLUSION: Higher prolactin levels were observed in infertile women with more severe endometriosis when compared to infertile women without endometriosis. Prolactin levels act as a probable prognostic biomarker to detect endometriosis stages III/IV vs. I/II and segregate infertile women with endometriosis from subjects without endometriosis.

Reproductive outcomes of vitrified blastocyst transfer in modified natural cycle versus mild hormonally stimulated and artificial protocols: A randomized control trial.

OBJECTIVE: This study set out to investigate the pregnancy outcome of natural cycle regimen versus other endometrial preparation protocols with vitrification thawed blastocyst transfer (VTBT) cycles. METHODS: This control trial study was carried out on 123 women undergoing VTBT. The women were randomly divided into three groups of endometrial preparation before VTBT; 1. Modified natural ovulation cycle with using HCG (n=32) 2. Mild hormonally stimulated cycle by low dose Clomiphene Citrate (n=30) and 3. Artificial cycle induced with estradiol and progesterone supplementation (n=61). Following endometrial preparation, the thawed blastocyst was vitrified and transferred. Reproductive outcome and endometrium characteristic were evaluated in the three groups. RESULTS: The three above-mentioned protocols resulted in clinical pregnancy rates of 21.43% vs. 13.79% vs. 15.25%, respectively; without statistical differences. The ongoing pregnancy rates did not show any significant differences among the three groups (21.43% vs. 13.79% vs. 13.56%), respectively. In addition, the miscarriage rates were compared in the three groups. The endometrial thickness on the day of progesterone or human chorionic gonadotropin administration were more frequently observed in the artificial and modified natural cycle versus hormonally stimulated groups (8.34±0.89 vs. 7.3±1.4, p<0.001; 8.13±0.95 vs. 7.3±1.4, p<0.001). There was no significant difference regarding triple-line endometrial patterns in the three groups. CONCLUSION: The natural cycle with HCG trigger could be considered as an alternative protocol to mild hormonally or artificial cycle regimens in vitrification thawed blastocyst transfers.

Azoospermia and testicular biopsy before intra-cytoplasmic sperm injection: Does the type of anesthesia make a difference?

AIM: Azoospermia is the most common form of male factor infertility, due to which sperms are retrieved for intra-cytoplasmic sperm injection (ICSI) under general or local anesthesia. The aim of the present study was to compare the efficacy of general and local anesthesia in an attempt to extract a sufficient quality of sperm for men with azoospermia, who intend to undergo ICSI. MATERIALS AND METHODS: A total number of 50 patients with azoospermia, who were within the age range of 20-40, were randomly scheduled for testicular sperm extraction with either general or local anesthesia before ICSI. The hormonal abnormalities and severe varicocele were evaluated and treated before the testicular sperm extraction. The inclusion criteria obliged the researchers to focus on men with azoospermic, those who were diagnosed by two semen analyses after a 3-day abstinence from coitus according to the modified WHO criteria, and 19< body mass index ≤28. The concentration, motility, and morphology of the spermatozoa of the two groups were also compared. RESULTS: A total number of 76 men, with a mean age of 35.1 ± 6.0, were selected, 26 were excluded from the study, and the remaining participants were randomly divided into two groups such as general anesthesia and lidocaine group. According to the results, the differences between the values of sperm parameters within various hours after the testicle biopsy were not statistically significant. Also, there was no significant difference between the two groups in terms of sperm motility and sperm morphology during various timing after the processing. CONCLUSION: The present study demonstrated that there was no evidence found for values of sperm parameters between the two groups, undergoing local and general anesthesia, within various hours after the testicular biopsy. Further investigations with more focus on concentration-dependent lidocaine on human sperm parameters need to be carried out.

Women's satisfaction in early versus delayed postcaesarean feeding: A one-blind randomized controlled trial study.

BACKGROUND: The early postoperative feeding after caesarean section (C- section) has remained controversial. This study was designed to evaluate the safety and efficacy of early versus delayed postcaesarean section oral feeding regarding gastrointestinal complications and patients postoperative satisfaction after C- section. METHODS: This clinical trial study was conducted on 200 pregnant women undergoing planned C-section under spinal anesthesia (Registration Number: IRCT: 138712211760N1). Women were randomly divided in two groups; group A (early feeding group) comprised of 101 patients who were encouraged to take oral fluid. If they tolerated, they continue semi-solid and solid foods starting 2 h after caesarean section. Group B (delayed feeding group) comprised of 99 patients who were given oral fluid 8 h after surgery. After beginning of feeding the patients' tolerance, first flatus, first defecation, beginning of regular diet, the length of hospital stay and also patient satisfaction level were evaluated in each group by visual scale analog (VAS). RESULTS: The mean time of the first passage of flatus was 10.2±1.7 hours for the early oral feeding group versus 10.7±1.6 hours for the delayed feeding group and the difference was significant (P=0.03). Duration to first defecation and length of hospital stay as well as patient satisfaction level did not differ significantly between the two groups. CONCLUSION: The results of this study suggest early postcaesarean feeding. It is well tolerated and helps return normal feeding habits.

Effect of Metformin and Flutamide on Anthropometric Indices and Laboratory Tests in Obese/Overweight PCOS Women under Hypocaloric Diet.

BACKGROUND: This study was designed to investigate the effect of metformin and flutamide alone or in combination with anthropometric indices and laboratory tests of obese/overweight PCOS women under hypocaloric diet. METHODS: This single blind clinical trial was performed on 120 PCOS women. At the beginning, hypocaloric diet was recommended for the patients. After one month while they were on the diet, the patients were randomly divided in 4 groups; metformin (500 mg, 3/day), flutamide (250 mg, 2/day), combined, metformin (500 mg, 3/day) with flutamide (250 mg, 2/day) and finally placebo group. The patients were treated for 6 months. Anthropometric indices and laboratory tests (fasting and glucose-stimulated insulin levels, lipid profile and androgens) were measured. A one-way ANOVA (Post Hoc) and paired t-test were performed to analyze data. A p ≤ 0.05 was considered statistically significant. RESULTS: After treatment, reduction in weight, BMI, hip circumference was significantly greater in the metformin group in comparison to other groups (p<0.05). In addition, the fasting insulin was significantly greater in metformin group and flutamide group in comparison to metformin+flutamide and placebo groups after treatment (p<0.05). Within groups, insulin level showed significant changes (before and after treatment) in metformin+flutamide group and LDL reduction was significant in flutamide group before and after treatment. Post hoc tukey and two-tailed with p≤0.05 were used to define statistical significance. CONCLUSION: Using combination of metformin and flutamide improves anthropometric indices and laboratory tests in obese/overweight PCOS women under hypocaloric diet.