The effect of normalizing vaginal microbiome using Lactovag in improving pregnancy outcomes in frozen embryo transfer cycles: a randomized clinical trial.

INTRODUCTION: Successful frozen-thawed embryo transfer (FTET) depends on multiple factors among which the woman's vaginal microbiota has recently been considered important. Using probiotic products, such as Lactovag in infertile women, the vaginal microbiome can become close to the healthy status. OBJECTIVES: The aim of this study was to evaluate the effect of Lactovag on normalizing vaginal microbiome, as well as its role in improving pregnancy outcomes in FTET cycles. PATIENTS AND METHODS: This randomized blinded clinical trial was conducted on 103 patients undergoing Assisted Reproductive Technology (ART) treatment at a tertiary university-based hospital between January and August of 2019. In the experiment group, the vaginal suppository Lactavag was prescribed, whereas in the control group, patients did not receive any microbiome supplements. Then, the pregnancy rate was compared in the two groups. RESULTS: There were no significant differences in baseline characteristics between the two study groups (p > 0.05). Positive B hCG was present in 28% (n = 26) of women, clinical pregnancy was achieved in 23.4% (n = 22) of them and fetal heart rate was detected in 21.3% (n = 20). These proportions were higher in the Lactovag group, although these differences were not significant (p > 0.05). Results showed that although transferring fetuses with grade A increased the odds of pregnancy with 1.53 (p = 0.001) folds, this ratio would be improved using Lactovag;1.68 (P value = 0.008). CONCLUSIONS: It seems that the vaginal microbiota critically interplays with women's health and reproduction. A probiotic agent such as Lactovag can be useful in normalizing this environment and improving pregnancy outcomes in infertile women.

Paradoxical air embolism in patients undergoing hysteroscopic surgery for cesarean scar pregnancy: A case report and review of the literatures.

Cesarean scar pregnancy cases who undergo hysteroscopic suction aspiration could be at higher risk of air emboli due to dilated, low-resistant, high-velocity blood vessels.

The effect of methyltestosterone on in vitro fertilization outcomes: A randomized clinical trial on patients with low ovarian response.

OBJECTIVE: The aim of this study was to compare the outcomes of in vitro fertilization (IVF) in patients with a poor ovarian response who used methyltestosterone, versus those using a placebo, in an infertility clinic setting. METHODS: This clinical trial included 120 women who had undergone IVF with intracytoplasmic sperm injection due to poor ovarian reserve and infertility. The study took place at the Yas Infertility Center in Tehran, Iran, between January 1, 2018 and January 1, 2019. In the intervention group, 25 mg of methyltestosterone was administered daily for 2 months prior to the initiation of assisted reproductive treatment. The control group was given placebo tablets for the same duration before starting their cycle. Each group was randomly assigned 60 patients. All analyses were performed using SPSS ver. 23 (IBM Corp.). RESULTS: The endometrial thickness in the intervention group was 7.57±1.22 mm, whereas in the control group, it was 7.11±1.02 (p=0.028). The gonadotropin number was significantly higher in the control group (64.7±13.48 vs. 57.9±9.25, p=0.001). However, there was no significant difference between the two groups in the antral follicular count. The chemical and clinical pregnancy rates in the intervention group were 18.33% and 15% respectively, compared to 8.33% and 6.67% in the control group. The rate of definitive pregnancy was marginally higher in the intervention group (13.3% vs. 3.3%, p=0.05). CONCLUSION: The findings of this study suggest that pretreatment with methyltestosterone significantly increases endometrium thickness and is associated with an increase in the definitive pregnancy rate.

Association study of the complement component C4 gene and suicide risk in schizophrenia.

Schizophrenia is a severe mental illness and a major risk factor for suicide, with approximately 50% of schizophrenia patients attempting and 10% dying from suicide. Although genetic components play a significant role in schizophrenia risk, the underlying genetic risk factors for suicide are poorly understood. The complement component C4 gene, an immune gene involved in the innate immune system and located in the major histocompatibility complex (MHC) region, has been identified to be strongly associated with schizophrenia risk. In addition, recent findings have also suggested that the MHC region has been associated with suicide risk across disorders, making C4 a potential candidate of interest for studying suicidality in schizophrenia patients. Despite growing interest in investigating the association between the C4 gene and schizophrenia, to our knowledge, no work has been done to examine the potential of C4 variants as suicide risk factors in patients with schizophrenia. In this study, we investigated the association between different C4 copy number variants and predicted C4 brain expression with suicidal outcomes (suicide attempts/suicidal ideation). We directly genotyped 434 schizophrenia patients to determine their C4A and C4B copy number variants. We found the C4AS copy number to be marginally and negatively associated with suicide risk, potentially being protective against suicide attempts (OR = 0.49; p = 0.05) and suicidal ideation (OR = 0.65; p = 0.07). Furthermore, sex-stratified analyses revealed that there are no significant differences between males and females. Our preliminary findings encourage additional studies of C4 and potential immune dysregulation in suicide.

Effect of intramuscular injection of human chorionic gonadotropin on endometrium preparation in frozen-thawed embryo transfer cycle: A randomized clinical trial.

Background: Assisted reproductive therapy (ART) has been developed remarkably in these decades; however, the rate of unsuccessful embryo implantation especially in the frozen-thawed embryo transfer (FET) cycles remains high and is reported up to 70%. The current study was designed to compare the effect of intramuscular injection of hCG on endometrium preparation and embryo implantation, in women undergoing FET compared to the control group. Methods: This clinical trial was done on 140 infertile women that underwent FET. The study sample was randomly allocated to the intervention group (two 5000 unit ampoules of hCG were injected intramuscularly before the first dose of progesterone administration) and the control group (without hCG injection). In both groups, 4 days after progesterone administration, the cleavage stage embryos were transferred. The study outcomes were biochemical pregnancy, clinical pregnancy and abortion rate. Results: The average age of intervention and control group was 32.65±6.05 and 33.11±5.36 years, respectively. The basic information between two study groups did not differ significantly. The chemical (30% vs. 17.1%, P=0.073, relative risk (RR)=0.57) and clinical (28.6% vs. 14.3%, P=0.039, RR=0.50) pregnancy rates were higher in the intervention group compared to the control group; these higher ratios were only significant in clinical pregnancy rate. Abortion rate was not significantly (P=0.620) different between the intervention and control groups (4.3% vs. 1.4%, respectively). Conclusion: This study showed that intramuscular injection of 10000 IU hCG before the endometrial secretory transformation phase in cleavage-stage embryo, improves IVF cycle outcomes.

Effect of intra-ovarian platelet rich plasma in women with poor ovarian response.

Background: Poor ovarian responder (POR) women, whose ovarian response to gonadotropin stimulation has decreased, are at higher risk of unsuccessful in-vitro fertilization (IVF). Therefore, this study designed to evaluate the effect of intra-ovarian platelet rich plasma (PRP) on POR women. Methods: This single-arm trial research was done on 20 POR women referred to the IVF Unit, university-based hospital, Tehran, Iran between October 2020 and September 2021. For all participants, autologous PRP was injected into each ovary by transvaginal ultrasound guidance under spinal anesthesia between days 12 and 14 of the menstrual cycle. After 12 weeks of PRP injection, embryo transfers were carried out following our routine IVF department protocol. The study outcomes were the number of mature oocytes, and pregnancy rates. Results: The average age of the participants was 41.80±1.82 yr. The average infertility duration was 9.70±1.89 yrs., with 80% primary infertility type. After PRP injection, follicle-stimulating hormone levels dropped about 1% (P=0.499), anti-Mullerian hormone levels were on average 4.5% higher (P=0.356), and estradiol levels raised by 1.2% (P=0.681). The average number of oocytes and their quality increased after PRP injection, while these changes were not significant (p-value>0.05). Chemical pregnancy was detected in 3 (15%) women and clinical pregnancy was detected only in one person. Conclusion: This study revealed that PRP injection into ovaries of POR women is safe and had a tendency to improve ovarian reserve markers and serum levels of AMH, estradiol, number and quality of oocytes.

User Experiences of Pharmacogenomic Testing and Opinions among Psychiatry Patients.

Pharmacogenomic testing (PGx) is a tool used to guide physicians in selecting an optimal medication for clients based on their genetic profile. The objective of this qualitative study is to understand patients' experiences with PGx testing as well as their opinions regarding the clinical adoption of such tests in psychiatry. A focus group was conducted to assess the needs of clients who had experience using a PGx test. Participants were recruited from a large study on PGx testing that offered physicians an opportunity to use PGx reports to guide psychotropic prescriptions. The focus group discussions were recorded, transcribed, and coded using NVivo to identify core themes. A total of 11 people participated in the focus group. Our analysis revealed that many participants were in favour of implementing PGx testing in psychiatric practice, and all expressed important considerations for patient-centred optimization of PGx testing. The main themes captured were: education and awareness among clinicians, cost considerations, PGx results-sharing and accessibility, and prospective benefits. The results of this study suggest that patients are keen to see PGx testing in widespread clinical care, but they report important opportunities to improve knowledge mobilization of PGx testing.

Co-treatment of gonadotropin and letrozole in infertile women with endometriosis: A double-blind randomized clinical trial.

Background: The common causes of infertility in women with endometriosis are folliculogenesis alternation, steroidogenesis and fertilization impairment, oocyte and embryo quality reduction, and implantation defect. Objective: To compare in vitro fertilization (IVF) cycle success rates of women with endometriosis who were treated with letrozole + gonadotropin (LA) vs. placebo + gonadotropin (PA). Materials and Methods: This double-blind, randomized clinical trial study was conducted with 94 infertile women with endometriosis (47 in the LA group and 47 in the PA group) who were candidates for IVF, from April-June 2021. For all participants, the long agonist protocol was applied. In both groups, gonadotropin-releasing hormone agonist was prescribed in the mid-luteal stage and from the third day of the cycle, and gonadotropin was started and its doses were regulated based on the patient's age, serum anti-Mullerian hormone and follicle-stimulating hormone. From the third day of the menstrual cycle, 5 mg of letrozole daily for 5 days was prescribed for the LA group, while the placebo was prescribed for the PA group on the identical days and duration. After embryo transfer, biochemical and clinical pregnancy were measured in the 2 groups. Results: The gonadotropin dosage (p < 0.01) and estradiol level (p = 0.02) on the human chorionic gonadotropin administration day were significantly lower in the LA group compared with in the PA group. Fetus transfer was done for 32 women. No significant differences were detected between the study groups regarding biochemical or clinical pregnancy (p = 0.72 for both). Conclusion: Letrozole as a co-treatment drug in the IVF cycle of women with endometriosis can significantly reduce the gonadotropin dosage and estradiol level with the same pregnancy rates.

The Effective Role of Adding Letrozole to Methotrexate in the Management of Tubal Ectopic Pregnancies, a Randomized Clinical Trial.

Ectopic pregnancy (EP) is considered a main reproductive health challenge. According to the side effects of using methotrexate (MTX), it is rational to find safer drugs in the management of EP. This randomized controlled trial aimed to evaluate the efficacy and safety of adding letrozole to the single-dose MTX in the management of EPs. This study was conducted in an academic hospital affiliated to Tehran University of Medical Sciences. Women with EP and stable vital signs with ß-hCG levels ≤3500 were assigned randomly to receive MTX + placebo or MTX + letrozole. The regression pattern of ß-hCG, need for further surgery, and potential side effects were compared between groups. A total of 90 women were assigned equally to the study groups and were matched in age, body mass index (BMI), serum biochemistry, and primary levels of ß-hCG. No drug-related side effects were observed in groups. The rates of further surgery (p = 0.614) and second dose of MTX (p = 0.809) were not significant between groups. In the MTX + placebo group, we observed a minor increase in ß-hCG levels on day 4 followed by a decreasing pattern on days 7 and 14. But, in MTX + letrozole group, a decreasing pattern in ß-hCG levels from day 1 through day 14 was perceived. The results support using MTX + letrozole to treat stable women diagnosed with tubal EP as a safe and efficient method. Further studies are required to evaluate letrozole alone as an alternative therapy in EPs.

The effect of vitamin D status on ovarian reserve markers in infertile women: A prospective cross-sectional study.

BACKGROUND: Vitamin D deficiency and infertility are two important health problems in Iran. Some studies suggest that vitamin D may influence Anti-Müllerian hormone (AMH) and antral follicle count (AFC) as an ovarian reserve. OBJECTIVE: The present study aimed to investigate the impact of vitamin D on AMH serum concentrations/AFC. MATERIALS AND METHODS: Three hundred and five infertile women referred to the IVF Unit of Yas hospital, between July and December 2017, were enrolled in this cross-sectional study. The demographic characteristics of the participants, as well as the serum levels of vitamin D, AMH, and ultrasonic examination of AFC were recorded. RESULTS: Finally, 287 infertile women were included in the analysis with a mean age of 29.95 ± 4.73 yr (18-45 yr) and a mean Body mass indexof 25.11 ± 4.41 kg/m 2 . The median AMH and vitamin D levels were 3.20 and 22.82 ng/ml, respectively. Considering the cut-off level of 20 ng/ml, 58.7% were vitamin D deficient. Regression analysis showed no association between AMH and vitamin D levels (p = 0.161), even after adjusting for baseline variables (p = 0.182). A total of 120 patients had an AFC < 6 and 164 ≥ 6, which was not statistically different between the groups with normal level or deficient vitamin D (p = 0.133). CONCLUSION: The present cross-sectional study showed no significant association between serum levels of vitamin D and AMH or AFC in infertile women, even after adjusting for baseline variables.

Timing of Elective Cesarean Section and Growth and Psychomotor Developmental Indices in 6-Month-Old Infants.

BACKGROUND: In the present study, we evaluated post-natal growth and psychomotor development status of infants at 6 months of age based on their gestational age at elective cesarean sections. METHODS: This is a prospective cohort study performed in 2014-2015 in Iran. The study population consisted of 6-month-old infants with gestational ages of 38-40 weeks delivered by elective cesarean section. The subjects were divided into 3 groups: Group A (neonates with gestational age of 380/7 weeks), group B (neonates with gestational age of 390/7 weeks), and group C (neonates with gestational age of 406/7 weeks). At the infant age of 6 months, the mothers were called for follow-up visits. Growth and psychomotor status of all subjects were assessed by expert pediatricians based on the Age and Stage Questionnaires. Recorded data related to outcomes in neonatal period and 6 months later were analyzed to determine associations between groups' variables. RESULTS: A total of 952 subjects were found eligible for study participation. The mean birth weight, length and head circumference were significantly higher in group C compared with the other groups (P=0.005). Regarding growth parameters, a significant association was found between gestational age at birth and all other growth indices at 6 months of age (P=0.005). The mean weight at 6 months of age was higher in group B in comparison with group A (P=0.001) and C (P=0.007). Infants born at 380/7 weeks were shorter in comparison with those born at 390/7 (P=0.002) and 406/7 weeks (P=0.005). Head circumference was significantly lower in group A than group B (P=0.02) and C (P=0.05). Regarding psychomotor indices at 6 months, a significant association was found between gestational age at birth and problem-solving skills (P=0.003). Delays in problem-solving skills were more frequent in neonates born at 380/7 weeks compared with those born at 390/7 (P=0.005) or 406/7 weeks (P=0.003). This difference was also significant between the two groups who were born at 390/7 and 406/7 weeks (P=0.01). CONCLUSION: The results from this study demonstrated that postponing the time of planned elective cesareans beyond 39 weeks of gestation may improve infant's growth and psychomotor outcomes.

Letrozole+ GnRH antagonist stimulation protocol in poor ovarian responders undergoing intracytoplasmic sperm injection cycles: An RCT.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) antagonist protocol has been proposed as a potentially proper option for the patients with limited ovarian reserve. Nevertheless, there is no significant difference in terms of clinical pregnancy between the GnRH antagonist and agonist cycles. The use of aromatase inhibitors such as letrozole was suggested by some studies. OBJECTIVE: The object of this study was to evaluate the efficacy of letrozole co-treatment with GnRH-antagonist protocol in ovarian stimulation of poor responder patients undergoing intracytoplasmic sperm injection. MATERIALS AND METHODS: A double-blinded randomized control trial was conducted on 70 infertile women with poor ovarian response based on Bologna criteria in two groups: letrozole+GnRH-antagonist (LA) group and placebo+GnRH-antagonist (PA) group (n=35/each). The LA group involved at letrozole 2.5 mg daily over 5 days and recombinant human follicle stimulating hormone 225 IU/daily. The PA group received placebo over 5 days and recombinant human follicle stimulating hormone at the same starting day and dose, similar to LA group. GnRH-antagonist was introduced once one or more follicle reached ≥14 mm. The main outcome measures were the number of oocytes retrieved, fertilization rate, implantation rate, cycle cancellation rate, and clinical pregnancy rate. RESULTS: There were no significant differences in demographic characteristics between groups. There were no significant differences between groups regarding the number of oocytes retrieved (p=0.81), number of embryos transferred (p=0.82), fertilization rate (p=0.225), implantation rate (p=0.72), total cycle cancelation rate (p=0.08), and clinical pregnancy rate (p=0.12). CONCLUSION: The use of letrozole in GnRH-antagonist cycles does not improve clinical outcomes in poor responder patients undergoing intracytoplasmic sperm injection.

The role of autoimmunity in premature ovarian failure.

Premature ovarian failure (POF) is a heterogeneous syndrome with several causative factors. Autoimmune mechanisms are involved in pathogenesis of 4-30 % of POF cases. The present review focuses on the role of autoimmunity in the pathophysiology of POF. The evidences for an autoimmune etiology are: demonstration of ovarian autoantibodies, the presence of lymphocytic oophoritis, and association with other autoimmune disorders. Several ovarian antigenic targets have been identified in POF patients. The oocyte seems to be the most often targeted cell. Lymphocytic oophoritis is widely present in POF associated adrenal insufficiency. Addison's disease is one of the most common autoimmune disorders associated with POF. Early detection of this potentially life threatening disease was recommended in several studies. The gold standard for detecting autoimmune POF is ovarian biopsy. This procedure is not recommended due to unknown clinical value, expense, and risks. Several immunoassays have been proposed as substitute diagnostic tools. Nevertheless, there is no clinically proven sensitive and specific serum test to confirm the diagnosis of autoimmune POF or to anticipate the patient's chance of developing POF or associated diseases. Some authors suggested the possible effects of immuno-modulating therapy on the resumption of ovarian function and fertility in a selected group of autoimmune POF patients. However, in most instances, this treatment fails to reverse the course of the disease. Numerous studies illustrated that standard treatment outcome for infertility is less effective in the presence of ovarian autoimmunity. The antibody-induced damage could be a pathogenic factor. Nevertheless, the precise cause remains obscure.

Simultaneous serous cyst adenoma and ovarian pregnancy in an infertile woman.

Ovarian pregnancy is a rare form of extra uterine pregnancy. Serous cyst adenoma is a benign variant of epithelial cell tumors of ovary. The coexistence of a cyst adenoma with an ovarian pregnancy in the same ovary is extremely rare. Some studies suggested that infertility or ovulation-inducing drugs can be involved in increased risk of ovarian tumors and ovarian pregnancies. A 28-year-old infertile woman presented with a ruptured ovarian pregnancy following ovulation induction with metformin. She had a concurrent benign serous cyst adenoma in the same ovary. Resection of both ovarian pregnancy and tumoral mass were performed. The ovary was preserved. Removal of gestational tissue and preservation of the involved ovary are the best options for management of ovarian pregnancy in young patient. Although there is an association between infertility/ovulation inducting medications and ovarian gestation, their connections with serous cyst adenoma are undetermined.

Pathogenesis and causes of premature ovarian failure: an update.

Premature ovarian failure (POF) affects 1% of young women. This condition has significant psychological sequelae and major health implications. POF seriously interferes with fertility and family planning. Diverse etiologies are associated with POF. Literature review related to the causes and pathogenesis of POF, cited between the year 1900 and May 2010. POF may be either spontaneous or induced. The known causes include: Genetic disorders, which could involve the X chromosome or autosomes. However, the growing body of literature demonstrates a list of newly discovered mutations that may be responsible for causing POF. Most of these mutations are extremely rare, and most cases of POF are still considered to be idiopathic.Autoimmune causes; there is some evidence of an association of POF with lymphocytic oophoritis and other autoimmune disorders. Antiovarian antibodies are reported in POF, but their specificity and pathogenic role are obscure.Iatrogenic causes; chemotherapy, radiotherapy and pelvic surgery can lead to POF.Infectious Causes; some viral and microbial infections can be followed by POF.Environmental toxins, such as cigarette smoking are reported as risk factors of spontaneous POF.Idiopathic; in most cases, no identifiable etiology can be recognized after complete evaluation.

A case report of spontaneous pregnancy during hormonal replacement therapy for premature ovarian failure.

BACKGROUND: Premature ovarian failure (POF) is a common condition; its incidence is estimated to be as great as 1 in 100 by the age of 40 years. Physiologic replacement of ovarian steroid hormones seems rational until the age of normal menopause. Temporary return of ovarian function and pregnancy may occur rarely in women with POF. We report a case of POF who conceived during hormone replacement therapy. CASE: A 30 years-old woman with confirmed POF after pelvic surgery and sever emotional stress conceived spontaneously. CONCLUSION: Return of ovarian function and achievement of pregnancy is possible in women with POF.

Controlled ovarian hyperstimulation and intrauterine insemination cycles in patients with unilateral tubal blockage diagnosed by hysterosalpingography.

BACKGROUND: Controlled ovarian hyperstimulation and intrauterine insemination (IUI) cycle is an ideal protocol for some subfertile patients. So, we decided to try this therapeutic protocol for the patients with unilateral tubal blockage diagnosed by hysterosalpingography (HSG). OBJECTIVE: To evaluate the effect of unilateral tubal blockage diagnosed by HSG on cumulative pregnancy rate (CPR) of the stimulated IUI cycles. MATERIALS AND METHODS: A cross-sectional analysis was performed between October 2006 and October 2009 in an academic reproductive endocrinology and infertility center. Two groups of patients undergoing stimulated IUI cycles were compared. Sixty-four infertile couples with unilateral tubal blockage diagnosed by HSG as the sole cause of infertility in the group (І), and two hundred couples with unexplained infertility in the group (II). The patients underwent 3 consecutive ovarian hyperstimulation (Clomiphen citrate and human menopausal gonadotropin) and IUI cycles. The main outcome measurements were the CPRs per patients for 3 consecutive stimulated IUI cycles. RESULTS: Cycle characteristics were found to be homogenous between the both groups. CPRs were similar in group І (26.6%) and group II (28%) (p=0.87; OR=1.075; 95% CI: 0.57 -2.28). CONCLUSION: Unilateral tubal blockage (diagnosed on HSG) has no effect on success rate of stimulated IUI cycles, so COH and IUI could be recommended as the initial therapeutic protocol in these patients.