The Value of Routine Hysteroscopy before the First Intracytoplasmic Sperm Injection Treatment Cycle.

BACKGROUND/AIMS: To assess uterine cavity with office hysteroscopy in order to diagnose and treat pathologies in patients who have started their first intracytoplasmic sperm injection (ICSI) cycles and evaluate its impact on pregnancy rate. METHODS: A number of 220 infertile women scheduled for ICSI participated in this prospective randomized study. They were randomly divided into 2 equal groups. Group I (intervention) underwent office hysteroscopy before starting assisted reproductive techniques (ART) cycle. Group II (control) started ART cycles without office hysteroscopy. All women had normal transvaginal ultrasonography and hysterosalpingography. The detected intrauterine abnormalities were treated during hysteroscopy. Four weeks after embryo transfer, ultrasonography was done for detecting clinical pregnancy. RESULTS: Abnormal findings were seen in hysteroscopy in 22.7% of the intervention group. The pregnancy rate in the intervention group (48.20%) was significantly higher than that in the control group (38.60%; p = 0.004). CONCLUSION: Routine office hysteroscopy before ICSI cycles provides direct evaluation of uterine cavity. Also, pregnancy rate improves after correction of endometrial cavity abnormalities.

Metformin treatment in different phenotypes of polycystic ovary syndrome.

BACKGROUND: The aim of this study was to evaluate the effectiveness of Metformin on ovulation and eventual clinical pregnancy in different phenotypes of polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: A total of 359 subjects who had proven PCOS according to Rotterdam criteria were prospectively selected. Patients' PCOS phenotypes were determined and recorded. All patients were younger than 35 years. Clinical and biochemical assays in all patients were initially obtained. Then patients were divided into two separate groups. One group received both 1,500 mg of Metformin and 1 mg of folic acid per day and the other group received only 1 mg of folic acid for a total of 2 months. Subsequently, all patients underwent ovulation stimulation with 5 mg of Letrozole per day for 5 days followed by an intra-uterine insemination. Finally, ovulation and pregnancy rates were evaluated for all four PCOS phenotypes. Effect of Metformin therapy was evaluated for each group and each phenotype. RESULTS: The pregnancy rate in Metformin and non-Metformin groups were, respectively, as follows: in phenotype A (39.2 vs. 33.7 %, p = 0.270), phenotype B (43.8 vs. 20 %, p = 0.210), phenotype C (44 vs. 20 %, p = 0.064), and phenotype D (36.5 vs. 28.6 %, p = 0.279). CONCLUSION: Although there was a little improvement in ovulation and pregnancy rates among patients with B and C phenotypes, there was not a statistically significant difference between the two groups. Based on our study, Metformin therapy does not change the ovulation and pregnancy rate.

Evaluation of sexual dysfunction prevalence in infertile couples.

INTRODUCTION: The physical health and emotional well-being of many individuals and couples of reproductive age are significantly affected by infertility. Sexual function is one of the important components of health and overall quality of life. AIMS: To determine the prevalence of sexual dysfunction in infertile couples. METHODS: In a cross-sectional study, in a tertiary university hospital, sexual dysfunction was assessed in 100 infertile couples. Sexual Function Questionnaire (SFQ) and International Index of Erectile Function (IIEF) questionnaire were administered. MAIN OUTCOME MEASURES: Prevalence of sexual dysfunction in infertile couples based on the score of the domains of SFQ and IIEF. RESULT(S): The SFQ score was within the normal range in all five domains in only 7% of women. The prevalence of female sexual dysfunction was highest and lowest in arousal-sensation (80.2%) and orgasm (22.8%) domains, respectively. Only 2% of male participants have had severe erectile dysfunction (ED). CONCLUSIONS: The prevalence of dysfunction in arousal-sensation and arousal-lubrication in our study was found to be higher than the results reported from Iranian normal population. The prevalence of any degree of ED in our study was higher than the prevalence reported for normal population and infertile men. The role of demographic factors, relationship parameters, and infertility per se in the prevalence of sexual dysfunction in infertile couples remains to be determined.

Effect of Increased Endometrial Thickness and Implantation Rate by Granulocyte Colony-Stimulating Factor on Unresponsive Thin Endometrium in Fresh In Vitro Fertilization Cycles: A Randomized Clinical Trial.

BACKGROUND: The correlation between endometrial thickness and receptivity has been mentioned in various studies. This study investigated the effect of granulocyte colony-stimulating factor in treating thin endometrium of infertile women who were chosen for in vitro fertilization in our infertility clinic in 2014 and 2015. METHODS: In this randomized clinical trial, 28 women who were chosen for in vitro fertilization and had endometrial thickness of less than 6 mm on the day of human chorionic gonadotropin (hCG) injection were included in the study. They were randomly divided into two groups: investigation and control groups. In investigation group (n = 13) one granulocyte colony-stimulating factor vial (300 micrograms in 1 mL) was infused into the uterus within five minutes by embryo transfer catheter. In control group (n = 15) 1 mL of saline was injected into the uterus with the same catheter. RESULTS: There were significant differences between the two groups in terms of means of endometrial thickness on oocyte retrieval day (P = 0.001), embryo transfer day (P = 0.001), hCG injections (P = 0.001), and implantation rates (P = 0.001). CONCLUSION: Granulocyte colony-stimulating factor can increase endometrial thickness in women treated with in vitro fertilization. RCT Code is 201406046063N2.

Modulation of steroidogenesis by vitamin D3 in granulosa cells of the mouse model of polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of women of reproductive age characterized by polycystic ovarian morphology, anovulation or oligomenorrhea, and hyperandrogenism. It is shown that disruption in the steroidogenesis pathway caused by excess androgen in PCOS is a critical element of abnormal folliculogenesis and failure in dominant follicle selection. Vitamin D plays an important role in the regulation of ovulatory dysfunction and can influence genes involved in steroidogenesis in granulosa cells. In the present study, we investigated the effects of vitamin D3 on steroidogenic enzyme expression and activities in granulosa cell using a PCOS mouse model. In our study, the PCOS mouse model was developed by the injection of dehydroepiandrosterone (DHEA) for 20 days. The mRNA and protein expression levels of genes involved in steroidogenesis in granulosa cells were compared between polycystic and normal ovaries using real-time PCR and Western blotting assays. Granulosa cells of DHEA-induced PCOS mice were then cultured with and without vitamin D3 and mRNA and protein expression levels of steroidogenic enzymes and serum 17beta-estradiol and progesterone levels were investigated using qRT-PCR, western blot, and radioimmunoassay, respectively. Steroidogenic enzymes including Cyp11a1, StAR, Cyp19a1, and 3ß-HSD were upregulated in granulosa cells of PCOS mice when compared to normal mice. Treatment with vitamin D3 decreased mRNA and protein expression levels of steroidogenic enzymes in cultured granulosa cells. Vitamin D3 also decreased aromatase and 3ß-HSD activity that leads to decreased 17beta-estradiol and progesterone release. This study suggests that vitamin D3 could modulate the steroidogenesis pathway in granulosa cells of PCOS mice that may lead to improving follicular development and maturation. This is a step towards a possible conceivable treatment for PCOS. ABBREVIATIONS: AMHR-II: anti-müllerian hormone receptor-II; 3ß-HSD: 3ß-hydroxysteroid dehydrogenase; Cyp11a1: Cytochrome P450 Family 11 Subfamily A Member 1; Cyp19a1: cytochrome P450 aromatase; DHEA: dehydroepiandrosterone; FSH: follicle stimulating hormone; FSHR: follicle stimulating hormone receptor; IVF: in vitro fertilization; 25OHD: 25-hydroxy vitamin D; OHSS: ovarian hyperstimulation syndrome; PCOS: polycystic ovarian syndrome; P450scc: P450 side-chain cleavage enzyme; StAR: steroidogenic acute regulatory protein; VDRs: vitamin D receptors.

The value of urea, creatinine, prolactin, and beta sub-unit of human chorionic gonadotropin of vaginal fluid in the diagnosis of premature preterm rupture of membranes in pregnancy.

OBJECTIVE: To evaluate the effectiveness of urea, creatinine, prolactin, and the beta sub-unit of human chorionic gonadotropin (ß-hCG) of vaginal fluid in the diagnosis premature preterm rupture of membranes (PROM). MATERIALS AND METHODS: In this observational study, 160 pregnant women with gestational age of 28 to 40 weeks were divided into two equal groups: investigation (documented PROM) and control (intact membrane) groups. Five cubic centimeters of normal saline was poured into the vagina of all participants and the liquid was extracted after a few minutes using a syringe. The liquid was sent to a laboratory for examination. Data were analyzed using a t-test. RESULTS: The volume of urea, creatinine, prolactin, and ß-hCG was significantly different in the two groups (p<0.001). Based on receiver operating characteristic curve and cut-off point, sensitivity, specificity, positive and negative predictive values of ß-hCG for detecting PROM were 87.5%, 86%, 86.4%, and 87.3%, respectively. Also, the same factors for urea in detecting PROM were 79.7%, 82.5%, 81.8%, and 80.4%, respectively. Creatinine had 74.6% sensitivity, 85% specificity, and 83% and 77.2% positive and negative predictive values for detecting PROM. Finally, prolactin had 87.5% sensitivity, 90% specificity, and 90% positive and 88% negative predictive values for detecting PROM. CONCLUSION: Prolactin and ß-hCG have more diagnostic value than urea and creatinine in detecting PROM, and can be used in suspected cases.

Hysteroscopy: A necessary method for detecting uterine pathologies in post-menopausal women with abnormal uterine bleeding or increased endometrial thickness.

OBJECTIVE: To investigate the histologic and hysteroscopic findings of post-menopausal women with uterine bleeding and asymptomatic women with increased endometrial thickness equal or more than 5 mm. MATERIALS AND METHODS: This cross-sectional study was performed between May 2014 and June 2015 on 110 post-menopausal women aged 40-82 years. The women were divided into two groups: Women with abnormal uterine bleeding (AUB group) and asymptomatic women with increased endometrial thickness (asymptomatic group). RESULTS: Among the participants, 67 women had AUB and 43 women were asymptomatic. In the AUB group sensitivity, specificity, and positive and negative predictive values of hysteroscopy for normal findings were 98%, 100%, 100% and 90%, respectively. In the asymptomatic group, the same parameters were 98%, 100%, 100% and 85%, respectively. The sensitivity, specificity, and positive and negative predictive values of hysteroscopy for polyps and myomas were 100%. Also, the sensitivity, specificity, and positive and negative predictive values were 100% in hyperplasia cases found during hysteroscopy in both groups. CONCLUSION: Increased endometrial thickness in postmenopausal women with or without AUB is mostly due to benign lesions such as polyps and submucosal myomas. Hysteroscopy is a safe and reliable method for evaluating and treating these lesions.

Pretreatment Beck Depression Inventory score is an important predictor for post-treatment score in infertile patients: a before-after study.

BACKGROUND: The experience of infertility can be extremely stressful. Some of the risk factors for depression in infertility are being female, repeated unsuccessful treatment cycles or a 2 to 3 year history of infertility, low socioeconomic status, foreign nationality, lack of partner support, life events and previous depression. In this study, we analyzed the Beck Depression Inventory score at the beginning and the end of infertility treatment, to determine which factors may influence the BDI score after treatment of infertility. METHODS: In a before-after study, in a university-affiliated teaching hospital, 251 women who had been visited for assisted reproductive technology infertility treatment participated in the study. BDI score was assessed before and after treatment of infertility. RESULTS: The mean BDI score rose after unsuccessful treatment and dropped after successful treatment. Those with lower education levels had a higher BDI score before treatment. BDI score after treatment was positively correlated with pretreatment BDI scoreand duration of infertility. CONCLUSION: BDI score after treatment was strongly connected to the BDI score before treatment, the result of therapy and to the duration of infertility. The influence of duration of infertility on BDI score after treatment of infertility is weak. So a simple method to screen patients at risk of depression after infertility treatment is determining pretreatment BDI score and predicting the result of infertility treatment by other risk factors.

Evaluation of Plasma Creatine Phosphokinase (CPK) Level Following a Single Injection of Methotrexate as a Predicator of Treatment Success in Ectopic Pregnancy.

OBJECTIVE: To evaluate the plasma creatine phosphokinase (CPK) level after a single injection of methotrexate (MTX) as a predictor of treatment success in ectopic pregnancy (EP). MATERIALS AND METHODS: In this prospective study, seventy nine women older than 18 years treated with methotrexate for ectopic pregnancy were evaluated for CPK and ß-subunit of human chorionic gonadotropin (ßhCG) levels, while they received intramuscular MTX at a dose of 50 mg/m2. The day of injection was considered as day 1 (D1). CPK level on D1 was compared between the group 1(as treatment success group), treated by a single MTX injection, and the group 2, treated by two or three MTX injections or by surgery. RESULTS: The success rate of MTX treatment was 58 (73.3%). The mean of CPK was higher in treatment success group (group1) than failure group (group 2) (71.98 ± 15.711 vs. 64.43 ± 15.898), but the difference was not significant (p=0.06). The mean of ßhCG was significantly lower in treatment success group (group 1) than failure group (group 2) (1187.52±631.45 vs. 1663.87±1096.845; p=0.01). Ultrasonographic findings of EP were seen in 63 patients, while the means of ßHCG and CPK were higher in these patients than those with normal ultrasonography, but difference was not significant (p=0.37 and p=0.24, respectively). CONCLUSION: The sample was not large enough to indicate a significant difference in the CPK level, which can be considered as an indicator for differentiating between the successful and unsuccessful treatment groups. Moreover, the present study did not show any relation between initial ß-hCG and CPK serum levels, so our findings indicate that they are not possibly considered as two independent biomarkers in ectopic pregnancy.

The effect of progesterone supplementation on pregnancy rates in controlled ovarian stimulation and intrauterine insemination cycles: a randomized prospective trial.

OBJECTIVE: To evaluate the effect of vaginal progesterone as luteal phase support on pregnancy rates in controlled ovarian stimulation and intrauterine insemination cycles in couples with unexplained or mild male factor infertility. STUDY DESIGN: 290 Patients who met the inclusion criteria were included in a prospective randomized controlled trial. All patients underwent controlled ovarian stimulation and intrauterine insemination: 148 patients were randomized to start with a supported cycle and 142 patients with an unsupported cycle. In supported cycles, patients received vaginal progesterone once daily from the day after insemination until 12 weeks of pregnancy or, in non-pregnant women, for 14 days. No progesterone was given during unsupported cycles. The main outcome measures were clinical pregnancy rates per cycle. RESULTS: In total, 148 cycles with luteal phase support and 142 cycles without luteal phase support were performed. The clinical pregnancy rates per cycle were higher for cycles with luteal phase support than for the unsupported cycles (24.3% vs. 14.1% respectively, p=0.027). CONCLUSION: The use of vaginal suppositories as luteal phase support significantly improved clinical pregnancy rates in controlled ovarian stimulation and intrauterine insemination in patients with unexplained or mild male factor infertility.

The Effect of Exercise in PCOS Women Who Exercise Regularly.

PURPOSE: To determine the prevalence of polycystic ovary syndrome (PCOS) in women who exercise regularly. METHODS: All women under age 45 from an industrial company who had past history of exercising more than 6 months enrolled in this cross-sectional study. Prevalence of PCOS and comparison of BMI between PCOS and non-PCOS subgroups was done. The diagnosis of PCOS was based on the revised 2003 Rotterdam ESHRE/ASRM consensus criteria and exclusion of related disorders. RESULTS: The prevalence of PCOS in was 8.8%; 95% CI: 8.5%-9.1%. In obese subjects, mean BMI differed significantly between PCOS and non-PCOS women (29.3 ±3.3 kg/m(2) vs. 27.8 ± 2 kg/m(2), P=0.03). In lean subjects, there was no statistically significant difference in terms of BMI between PCOS and non-PCOS women (21.4 ± 1.9 kg/m(2) vs. 21.2 ± 2 kg/m(2), P>0.05). CONCLUSION: Obese PCOS patients show more difficulty in losing weight by exercise than lean PCOS patients. The role of hormonal alterations and PCOS per se in the responsiveness of weight loss to exercise remains to be determined.

Clinical outcome with half-dose depot triptorelin is the same as reduced-dose daily buserelin in a long protocol of controlled ovarian stimulation for ICSI/embryo transfer: a randomized double-blind clinical trial (NCT00461916).

BACKGROUND: Traditional doses of depot GnRH agonist may be excessive for ovarian stimulation. We compared half-dose depot triptorelin (Group I) with reduced-dose daily buserelin (Group II) in a long protocol ICSI/embryo transfer through a double-blind randomized clinical trial. METHODS: Controlled ovarian stimulation (COS) was started by a pretreatment with oral contraceptives for 21 days. Then, 182 patients were randomized into two groups of 91. Group I received 1.87 mg triptorelin depot i.m. followed by daily s.c. injections of saline. Group II (reduced-dose protocol) received a bolus injection of i.m. saline followed by daily s.c. injections of 0.5 mg buserelin, which was then reduced to 0.25 mg at the start of human menopausal gonadotrophin stimulation. When transvaginal ultrasound showed at least two follicles of 16-20 mm diameter, HCG was given and ICSI was performed 40-42 h later. RESULTS: No significant differences were seen in the mean (SD) number of follicles at HCG administration, as our primary outcome [10.3 (4.4) in Group I versus 11.1 (4.2) in Group II, P = 0.180, mean difference = 0.86, 95% confidence interval 0.39-2.11]. The other early results of COS, clinical and ongoing pregnancy rates, or early pregnancy loss were also not significantly different between the groups. Group I endured longer stimulation period [11.2 (1.8) days versus 10.6 (1.9), P = 0.030]. CONCLUSIONS: Clinical outcomes were not significantly different between Group I and Group II.

Comparison of unilateral and bilateral transfer of injected oocytes into fallopian tubes: a prospective, randomized clinical trial.

OBJECTIVE: To assess whether pregnancy rate differs in unilateral vs. bilateral transfer in "immediate transfer of injected oocytes into the fallopian tubes." DESIGN: Prospective randomized clinical trial. SETTING: Tertiary university hospital. PATIENT(S): The study population included 160 patients presenting with male factor infertility who fulfilled the criteria for immediate transfer of injected oocytes into tubes. INTERVENTION(S): Four injected oocytes were transferred into two tubes (study group) or one tube (control group). MAIN OUTCOME MEASURE(S): Implantation rate, clinical pregnancy rate, multiple pregnancy rate, and incidence of pregnancy with unknown location (PUL). RESULT(S): A total of 72 (45%) pregnancies were achieved. There were 32 pregnancies (1 PUL, 4 multiple, and 27 singletons) in the bilateral transfer group and 40 pregnancies in the unilateral transfer group (1 PUL, 7 multiple, and 32 singletons). No significant difference was found in the implantation rate, clinical pregnancy rate, multiple pregnancy rate, and incidence of PUL. CONCLUSION(S): This study demonstrates that no difference in outcome occurred between unilateral and bilateral transfer in microinjected oocytes intrafallopian transfer (MIFT). Therefore, along with the same outcome parameters, unilateral transfer is the preferred method of MIFT.

Comparison of success rates in the medical management of ectopic pregnancy with single-dose and multiple-dose administration of methotrexate: a prospective, randomized clinical trial.

OBJECTIVE: To assess whether success rate differs in single-dose versus multiple-dose administration of methotrexate (MTX) in medical management of unruptured ectopic pregnancies. DESIGN: Prospective randomized clinical trial. SETTING: Tertiary university hospital. PATIENT(S): The study population included 108 patients presenting with unruptured ectopic pregnancies who fulfilled the criteria for medical management. INTERVENTION(S): A single dose (study group) or multiple doses (control group) of MTX were administered IM. MAIN OUTCOME MEASURE(S): Success rate of medical management in each group. RESULT(S): Of the 54 patients on the single-dose protocol, treatment was considered successful in 48 patients (88.9%). Of the 54 patients on the multiple-dose protocol, 50 participants responded to the treatment (92.6%). The difference between success rates in the two groups was not statistically significant (P=.7; odds ratio 0.64; 95% confidence interval 0.17-2.4). In the single-dose and multiple-dose groups, 15 (27.8%) and 20 (37%) patients, respectively, had complications (P=.3). CONCLUSION(S): The results of our study showed that single-dose treatment with MTX could be as successful as multiple doses. The incidence of complications did not differ between the two groups. It appears that single-dose treatment could be the first line of treatment in selected patients.

The effects of L-carnitine on sperm parameters in smoker and non-smoker patients with idiopathic sperm abnormalities.

PURPOSE: To determine the effects of L: -carnitine on sperm parameters in patients with idiopathic sperm abnormalities. METHODS: In an academic reproductive care center, 170 patients including 48 smokers and 122 non-smokers participated in a before-after study. Men were given 1 g of L: -carnitine orally 3 x daily for 3 months. Sperm assessment was done before and after the treatment. Main outcome measures were sperm concentration, motility, and morphology before and after the treatment. RESULTS: L-Carnitine was effective in improvement of percentile of motile sperms, grade A sperms, and normal-shaped sperms. L-Carnitine significantly improved percentile of motile and grade A sperms in non-smokers. Only the change in the median percentile of normal forms was within the significant range in smokers. CONCLUSIONS: The results of this study indicate that smoker patients should not be excluded from the treatment with L-carnitine based on smoking alone.