Effect of conditioned medium of umbilical cord-derived mesenchymal stem cells as a culture medium for human granulosa cells: An experimental study

Background: The umbilical cord-derived mesenchymal stem cells conditioned medium (UC-MSCs-CM) produces secretomes with anti-apoptotic properties, and has the potential to prevent apoptosis of granulosa cells (GC) during controlled ovarian hyperstimulation. Objective: To observe the effect of UC-MSCs-CM on the interaction between pro- and anti-apoptotic proteins and the influence of growth differentiation factor 9 (GDF9) production in GC. Materials and Methods: UC-MSCs-CM was collected from umbilical cord stem cell culture on passage 4. GC from 23 women who underwent in vitro fertilization were cultured and exposed to UC-MSCs-CM for 24 hr. Then RNA of the GC was extracted and the mRNA expression of BCL-2 associated X (BAX), survivin and GDF9 were analysed using quantitative real-time PCR. The spent culture media of the GC were collected for measurement of insulin growth factor 1 using ELISA. Results: The expression of BAX was significantly different after UC-MSCs-CM exposure (4.09E-7 vs. 3.74E-7, p = 0.02). No significant changes occurred in survivin, BAX/survivin ratio, and GDF9 expression after UC-MSCs-CM exposure (p > 0.05). The IGF-1 level of the CM was significantly higher after the CM was used as a culture medium for GC (2.28 vs. 3.07 ± 1.72, p ≤ 0.001). A significant positive correlation was found between survivin and GDF9 (r = 0.966, p ≤ 0.001). Conclusion: IGF-1 produced by UC-MSCs-CM can work in paracrine fashion through the IGF receptor, which can inhibit BAX and maintain GDF9 production. Moreover, under the influence of UC-MSCs-CM, GC are also capable of producing IGF-1, which can impact GC through autocrine processes. Key words: Conditioned medium, BAX, Survivin, GDF9, IGF-1.

The effect of cult-active medium on pregnancy outcomes after intracytoplasmic sperm injection in azoospermic men: A case-control study

Background: Failed oocyte activation following intracytoplasmic sperm injection (ICSI) as a result of calcium deficiency is a major challenge. Objective: We compared the effect of cult-active medium (CAM) on ICSI outcomes in obstructive azoospermia cases. Materials and Methods: The present study was conducted with 152 ICSI cases, classified into CAM and control groups. The injected oocytes in the control group were cultured in the cleavage medium, while in the artificial oocyte activation group, oocytes were chemically activated through exposure to 200 µL of CAM for 15 min. Fertilization and cleavage rates, quality of embryos, and biochemical pregnancy and live birth rates were assessed in both groups. Results: There were significant differences between the groups in terms of fertilization and cleavage rates after using the CAM in the percutaneous epididymal sperm aspiration (PESA) subgroup (p = 0.05, p ≤ 0.001) and in the testicular sperm extraction subgroup (p = 0.02, p = 0.04), compared to their control groups. Also, the pregnancy rate was significantly higher in the PESA-CAM subgroup (p = 0.03). The PESA-CAM subgroup demonstrated a significant difference in embryo quality after ICSI (p = 0.04). Unsuccessful embryo transfer and abortion were lower in both subgroups compared to the control groups, but this difference was not significant. Surprisingly, live birth rate was higher in the PESA-CAM subgroup (p = 0.03). Conclusion: CAM treatment could improve fertilization and cleavage rates in obstructive azoospermia participants. It had a significant effect on embryo quality, and pregnancy and live birth rates in PESA cases. Key words: Calcium ionophore, Obstructive azoospermia, Fertilization, ICSI.

Effect of silymarin and metformin on the sperm parameters and histopathological changes of testes in diabetic rats: An experimental study

Background: Oxidative stress is a major contributor to diabetes, which can lead to testicular damage and infertility. Objective: This study aimed to compare the effects of metformin as a chemical drug with silymarin as an herbal agent on the sperm parameters and histopathological changes of testes in diabetic rats. Materials and Methods: Thirty-two male Wistar rats (250-270 gr) were randomly divided into four groups: 1) control; 2) diabetic; 3) diabetic+metformin 200 mg/kg; and 4) diabetic+silymarin 100 mg/kg. Daily injections were administered intraperitoneally for 56 days. At the end of the treatment, blood sampling was performed for biochemical assessment. Then, the rats were sacrificed and their left testis and epididymis were cut for sperm analysis as well as histopathology and morphometric evaluation. Results: Diabetes was associated with a reduced sperm count, motility, viability, maturity, and chromatin quality of sperm (p ≤ 0.001). It was also associated with a higher malondialdehide level and lower total antioxidant capacity level of serum in comparison with the control group (p ≤ 0.001). There was a significant difference in the seminiferous tubule diameter, germinal epithelium height, and testicular histopathological alterations in the diabetic rats compared with the control rats (p ≤ 0.001). Treatment with metformin and silymarin improved the above-mentioned parameters and this improvement was more substantial in silymarin-treated animals (p ≤ 0.001). Conclusion: In diabetic rats, metformin and silymarin improved sperm parameters, sperm DNA integrity, seminiferous tubule diameter, germinal epithelium thickness, and testicular histopathological complications; this improvement was more substantial in the silymarin-treated group. So, the findings of this study suggest that silymarin is more effective than metformin in treating diabetic-induced infertility. Key words: Diabetes, DNA damage, Metformin, Silymarin, Sperm, Testis.

Evaluation of hyperprolactinemia risk factors in infertile women referred to Yazd Infertility Center: A cross-sectional study

Background: Hyperprolactinemia is one of the most common causes of infertility in women. The prevalence of pituitary tumors is 25-30% among infertile participants with hyperprolactinemia. Objective: The aim of this study was to describe the causes of hyperprolactinemia in infertile women referred to Yazd Infertility Center. Materials and Methods: This cross-sectional study was conducted with 182 infertile women with hyperprolactinemia who were referred to Yazd Infertility Center from February 2018 to October 2019. Serum prolactin was assessed by the human prolactin ELISA kit according to the Padtan Gostar Isar protocol. The age, duration of infertility, causes of hyperprolactinemia, and type of infertility treatment were noted. The MRI findings were added. Results: The mean age of participants was 28.9 ± 0.36 yr and the prolactin level was 76 ± 8.97 ng/ml. The etiology of hyperprolactinemia among the study participants was 35 participants (19.2%) with pituitary adenoma, 47 participants (25.8%) with polycystic ovary syndrome, 14 participants (7.7%) with pituitary adenoma and polycystic ovary syndrome, and 86 participants (47.3%) with idiopathic hyperprolactinemia. The results of this study showed that there was no statistically significant difference between the mean prolactin levels in participants with different causes of hyperprolactinemia (p = 0.31). Conclusion: Idiopathic hyperprolactinemia and polycystic ovary syndrome are the most common reasons for hyperprolactinemia. Key words: Hyperprolactinemia, Infertility, PCOS.

Maternal-fetal attachment and anxiety in pregnant women who conceived through assisted reproductive technology: A longitudinal study

Background: Pregnancy through assisted reproductive technology (ART) is a stressful experience that may affect prenatal attachment. However, maternal-fetal attachment (MFA) and anxiety in pregnancy after ART are understudied in Iran. Objective: To compare changes in MFA and pregnancy-related anxiety (PRA) in the first and third trimester of pregnancy in women who conceived through ART compared to those who conceived naturally. Materials and Methods: This longitudinal study was conducted in 2019 with 187 pregnant women (ART conception = 43, natural conception = 144). Participants were recruited using the consecutive sampling method from a prenatal clinic in Tehran. The Cranley MFA Scale and the Van Den Bergh PRA Questionnaire were used to collect the data. Results: The MFA score in the 12th wk of gestation was lower in the women who conceived with ART compared to in the women who conceived naturally, but there was no statistically significant difference between the groups in wk 36. MFA in both groups was significantly higher at gestational wk 36 than wk 12 (p ≤ 0.001). The increase in MFA score was significantly higher in the women who conceived with ART than in those who conceived naturally (p ≤ 0.001). The anxiety score declined in the two groups and no statistically significant difference was observed in the changes of anxiety scores between the two groups (p = 0.84). Conclusion: Pregnant women who conceived through ART were as attached to their fetus in the third trimester of pregnancy as other women and did not experience more PRA. Key words: Attachment, Maternal fetal relations, Assisted reproductive technology, Pregnancy, Anxiety.

Impairment of sperm efficiency in mice following short-term nano-titanium dioxide exposure: An experimental study

Background: Titanium dioxide nanoparticles (TiO2NPs) are widely used in many compounds. Recent evidence has displayed some cytotoxic effects of TiO2NPs on male reproduction. Objective: The effects of TiO2NP administration on sperm parameters and chromatin and seminiferous histopathology of male mice were investigated. Materials and Methods: In this experimental study, 32 NMRI male mice (35 ± 3 gr, 8-12-week-old) were divided into four groups (n = 8/each): treated groups were fed orally with 2.5 (group I), 5 (group II) and 10 (group III) mg/kg/day TiO2NPs for 40 days and the control group received phosphate buffered saline. Sperm parameters, DNA integrity and chromatin quality were assessed using chromomycin A3, aniline blue, toluidine blue staining and TUNEL. Hematoxylin eosin staining was performed to measure spermatogenic cells and the total diameter of seminiferous tubules. Also, sex hormone and malondyaldehyde levels were measured. Results: Abnormal sperm tails rose in group III (28.87 ± 4.91) in comparison with the control group (12.75 ± 3.95). However, chromomycin A3 staining and TUNEL showed higher levels in group III in comparison with the control group, whereas aniline blue and toluidine blue staining showed no differences. A significantly lower spermatogenesis index and lumen parameters were observed in group III. Leydig cell numbers, cellular diameters and the area of the seminiferous tubules were lower in the treated groups. The testosterone level was also lower in these groups and the percentage of malondyaldehyde in the seminal fluid was higher. Conclusion: Exact mechanisms of TiO2NPs are not clear; however, cytotoxic and genotoxic effects of TiO2NPs may relate to oxidative stress. Given their widespread use, TiO2NPs should be a public health focus of attention. Key words: Titanium dioxide, Spermatogenesis, Histology, Mouse, Chromatin, TUNEL.

Maternal polymorphic loci of rs1979277 serine hydroxymethyl transferase and rs1805087 5-methylenetetrahydrofolate are correlated with the development of fetal growth restriction: A case-control study

Background: Key reactions in folate-mediated single-carbon metabolism are regulated by folate cycle enzymes. Violations of the folate cycle may be associated with the occurrence of fetal growth restriction (FGR) in pregnant women. Objective: To study the relationship between polymorphisms of folate cycle genes in the mother with the development of FGR. Materials and Methods: In this case-control study, 122 pregnant women with FGR and 243 pregnant women with normal newborn weight were enrolled. The polymorphic loci of folate cycle genes including rs1805087 5-methylenetetrahydrofolate (MTR) and rs1979277 serine hydroxymethyl transferase (SHMT1) were examined. The study of polymorphisms was carried out through the TaqMan probe detection method using polymerase chain reaction. Logistic regression was used to analyze the associations of the polymorphisms. Results: It was established that the T allele rs1979277 of the SHMT1 gene was correlated with the development of FGR within the framework of the allelic (OR = 1.67, 95% CI 1.20-2.33, pperm < 0.01), additive (OR = 1.69, 95% CI 1.20-2.37, pperm < 0.01), dominant (OR = 1.81, 95% CI 1.15-2.87, pperm = 0.01) and recessive (OR = 2.34, 95% CI 1.15-4.73, pperm = 0.01) models. The association of the G rs1805087 allele of the MTR gene with the occurrence of FGR was also identified following the recessive model (OR = 3.01, 95% CI 1.05-8.68, pperm = 0.04). Conclusion: Our results indicated that maternal polymorphic loci rs1979277 SHMT1 and rs1805087 MTR may be associated with the development of FGR. Key words: Polymorphism, Associations, Fetal growth restriction, Folic acid.

PERMA model vs. integrative-behavioral couple therapy for fertility problems: A randomized clinical trial protocol

Background: Psychological interventions may reduce fertility problems. Positive emotion, engagement, meaning, positive relationship and accomplishment (PERMA) is a cognitive intervention and integrative-behavioral couple therapy (IBCT) is a behavioral intervention. Appropriate mental interventions are important in infertility treatment. Objective: To investigate the effect of the PERMA model vs. IBCT in reducing the fertility problems of couples. Materials and Methods: The content of the interventions was developed and adjusted based on a literature review and the opinions of experts. In this three-arm parallel randomized clinical trial, 42 couples undergoing infertility treatment will be allocated randomly into three groups (n = 14 couples/each). Group 1 will receive the PERMA intervention, group 2 will receive the IBCT intervention, and group 3 as the control group will receive an infertility treatment training program intervention. The primary outcome will be the fertility problems, which will be measured by completing a fertility problem inventory at baseline, as well as in the 5th and 9th wk as a follow-up. Another primary outcome, satisfaction with the intervention, will also be assessed in the 5th and 9th wk. The secondry outcome will be a positive pregnancy test at wk 12. The interventions will be conducted through a combination of face-to-face and online via WhatsApp. Conclusion: This study will assess social, sexual, and parenthood concerns. A combination of online and face-to-face interventions will be appropriate given the COVID-19 pandemic. Couple’s counseling may provide better counseling outcomes for fertility problems in comparison with group counseling. This study will try to optimize resilience during infertility treatment through learning better relationship and problem-solving skills, and may have an indirect impact on pregnancy rate, burden of infertility, and costs of treatment due to increased effectiveness. Key words: Online, Face-to-face, Infertility, Integrative-behavioral couple therapy, PERMA model, RCT, Positive psychology, Protocol study, COVID-19.

Differences in perinatal outcomes in teenage mothers with their first and third pregnancies and predictors of adverse neonatal events: A cross-sectional study

Background: Repeated teenage pregnancy is a major burden on the healthcare system worldwide. Objective: We aimed to compare teenagers with their first and third pregnancies and to evaluate the likelihood of neonatal complications. Materials and Methods: This cross-sectional study was performed on female teenagers (aged ≤ 19 yr) with singleton pregnancies. The subjects (n = 298) were screened over 12 months. Ninety-six women were excluded, based on the exclusion criteria. The remaining subjects (n = 202) were divided into two groups: teenagers with first pregnancy (n = 96) and teenagers with third pregnancy (n = 47). The subjects were observed throughout pregnancy and delivery. The final sample size of the first and third pregnancy groups was 96 and 47, respectively. Results: There was a significant risk of preeclampsia in the first pregnancy group (p = 0.01). Low birth weight, five-min Apgar score < 7, and neonatal intensive care unit admission were the most significant neonatal outcomes in the first pregnancy group. In the third pregnancy group, significant predictors of neonatal complications included very young age in the first pregnancy (≤ 15 yr), an inter-pregnancy interval < 2 yr, current anemia, and history of obstetric and/or neonatal complications in previous pregnancies. Conclusion: Based on the results, teenagers with their first pregnancy had comparable obstetric outcomes (except for preeclampsia) as teenagers with their third pregnancy, whereas neonatal complications occurred more frequently in the first pregnancy group. Overall, we can predict high-risk neonates in the third pregnancy, based on the abovementioned parameters. Key words: Teenage pregnancy, Complications, Neonate.

Corrigendum to “Comparing the effects of nursing versus peer-based education methods on the preoperative anxiety in infertile women: An RCT” [Int J Reprod BioMed 2019; 17: 883-890]

This is a Corrigendum to “Comparing the effects of nursing versus peer-based education methods on the preoperative anxiety in infertile women: An RCT” [Int J Reprod BioMed 2019; 17: 883-890] and does not have an abstract. Please download the PDF or view the article HTML.