Is there any role of interleukin-6 and high sensitive C-reactive protein in predicting IVF/ICSI success? A prospective cohort study.

OBJECTIVES: Studies have established a relationship between proinflammatory factors and implantation failure in IVF/ICSI cycles. Likewise, low-grade chronic inflammation is generally blamed for predisposing infertility. In the present study, we aimed to find a relationship between serum IL-6 and hs-CRP levels and IVF/ICSI cycle outcomes. METHODS: A total of 129 patients who consented to participate and attended the IVF unit of our department for the treatment of infertility have been enrolled in this prospective cohort study. Serum levels of high sensitive C-reactive protein and interleukin 6 have been detected at the beginning of the IVF/ICSI ovulation induction cycle. Cycle outcomes have been compared between patients with and without clinical pregnancy achievement following ART treatments. IVF/ICSI cycle outcomes of these two groups were also comparable except the number of >14 mm follicles, retrieved oocytes, metaphase II oocytes, and fertilized oocytes (2 pronuclei) which were in favor of the clinical pregnancy group. RESULTS: Mean serum hs-CRP levels were 3.08 mg/L (0.12-35.04) and 2.28 mg/L (0.09-22.52) patients with and without clinical pregnancy respectively. Mean serum IL-6 levels were 2 pg/mL (1-10.2) and 2 pg/mL (1-76.9) patients with and without clinical pregnancy respectively. Both tests were found to be statistically insignificant in predicting the success of the ART cycle in terms of implantation, clinical pregnancy, miscarriage, and live birth. CONCLUSIONS: In the present study, we have not found any significant effect of hs-CRP and IL-6 levels in the IVF cycle. However, in the light of this and previous studies, large-scale research may prove the exact influence of these markers on IVF success.

Comparison of two different starting doses of recombinant follicle stimulating hormone (rFSH) for intrauterine insemination (IUI) cycles in non-obese women with polycystic ovary syndrome (PCOS): a retrospective cohort study.

We aimed to compare the efficacy of two different starting doses of recombinant follicle stimulating hormone (rFSH), 37.5 vs. 75 international units (IU) for intrauterine insemination (IUI) cycles in non-obese women with polycystic ovary syndrome (PCOS). A total of 109 women who underwent first rFSH stimulated IUI cycle were included in this retrospective cohort study. The primary outcome measure was the clinical pregnancy rate. No significant difference was found in terms of clinical pregnancy rate between the two groups (22% for the 37.5-IU group and 24% for the 75-IU group, respectively, p = .808). There was no significant difference in monofollicular development rate among the groups (p = .354). The total rFSH consumption was lower in the 37.5-IU group compared to the 75-IU group (p< .001). There was no statistically significant difference in pregnancy rates between the 37.5-IU and 75-IU groups in both normal weight (BMI: 19-24.9 kg/m2) and overweight (BMI: 25-29.9 kg/m2) women (p = .889 and .518, respectively). These results suggest that the starting doses of 37.5 and 75 IU of rFSH do not show significant difference in clinical pregnancy rates in non-obese PCOS women undergoing IUI cycles.Impact StatementWhat is already known on this subject? Low-dose gonadotropin treatment is advised for women with polycystic ovary syndrome (PCOS). However, there are few comparative data on the efficacy of different starting doses of recombinant follicle stimulating hormone (rFSH) for intrauterine insemination (IUI) cycles in PCOS women.What the results of this study add? There was no statistically significant difference in pregnancy rates of non-obese patients with PCOS having IUI whether rFSH was started at 37.5 or 75 international units (IU).What the implications are of these findings for clinical practice and/or further research? A starting dose of 37.5 IU of rFSH may be a reasonable approach for IUI cycles in non-obese PCOS women.

The role of oxidative stress on subclinical atherosclerosis in premature ovarian insufficiency and relationship with carotid intima-media thickness.

Objective: We aimed to investigate the relationship between oxidative stress (OS) and subclinical atherosclerosis in patients with premature ovarian insufficiency (POI), by analyzing the dynamic thiol/disulfide homeostasis (TDH) parameters as an OS marker and carotid intima-media thickness (CIMT).Materials and methods: A total of 69 women, 34 with POI and 35 healthy controls were included in this prospective cross-sectional study. TDH parameters (plasma native thiol, total thiol, disulfide, disulfide/native thiol, native thiol/total thiol, and disulfide/total thiol ratios) and CIMT were measured and compared between the two groups.Results: In primary ovarian insufficiency group, native thiol (p=.009) and total thiol (p=.010) levels were significantly decreased, and CIMT values were significantly increased (p= <.001). CIMT values were negatively correlated with native thiol (r=-0.553, p=.001) and total thiol levels (r=-0.565, p=.001); and positively correlated with age (r = 0.457, p=.007), BMI (r = 0.408, p=.017), and total cholesterol (r = 0.605, p<.001) in POI group.Conclusions: Decreased native thiol and total thiol levels demonstrate the defective anti-oxidant mechanism in POI. Negative correlation between native thiol, total thiol levels, and CIMT means the presence of abnormal anti-oxidant mechanisms may play a role in the development of subclinical atherosclerosis in patients with POI. This is a novel report on the mechanism of subclinical atherosclerosis in women with POI, which needs to be supported with further studies evaluating the pathophysiology of OS.

The role of anti-Müllerian hormone in prediction of pregnancy in young and older women with unexplained infertility undergoing intrauterine insemination.

BACKGROUND: Serum anti-Müllerian hormone (AMH) level is considered to be a reliable marker of ovarian reserve. However, there are conflicting reports on the role of AMH level in predicting pregnancy after intrauterine insemination (IUI) cycles. The aim of this study is to investigate the clinical value of AMH in predicting pregnancy in younger and older women with unexplained infertility undergoing gonadotropin stimulation and IUI. METHODS: The medical records of 84 women who underwent first gonadotropin-stimulated IUI cycle owing to unexplained infertility were retrospectively evaluated. The relation of AMH levels with clinical pregnancy rate was analyzed. RESULTS: The overall clinical pregnancy rate was 19%. There was no significant difference in AMH levels between the pregnant and nonpregnant women (2.0 ± 1.0 vs 2.8 ± 2.0 ng/mL, respectively, p = 0.250). A further analysis according to age also failed to reveal significant differences in AMH levels between pregnant and nonpregnant women for both the younger (<35 years, n = 61) and the older (≥35 years, n = 23) subgroups (p = 0.714 and 0.532, respectively). Post-hoc power analysis showed a power of 0.80 with a 5% level of significance and a 0.8 effect size. CONCLUSION: These findings indicate that AMH levels cannot predict pregnancy in women with unexplained infertility undergoing gonadotropin-stimulated IUI cycle. In addition, AMH is not a strong predictive factor for pregnancy either in younger or older women.

Adnexal lesions after hysterectomy: A retrospective observational study

Objective: To characterize adnexal lesions detected in patients who had undergone previous hysterectomy with one or both ovaries conserved, and to define the clinical, pathologic, and surgical characteristics of the adnexal lesions in these patients. Material and Methods: A retrospective observational study was conducted on patients who had undergone a previous abdominal hysterectomy with one or both adnexa preserved and who had subsequently presented with an adnexal lesion. Characteristics of lesions, operative, and pathologic findings in patients who required a re-operation were noted. Results: One hundred thirty-seven patients presented with an adnexal lesion after hysterectomy. Of the 137 patients, 71 (51.8%) had undergone a re-operation (re-operated group), the rest of the patients (n=66, 48.1%) remained on follow-up (follow-up group) in whom the lesion disappeared during follow-up period. Adnexal lesions that were re-operated were significantly larger (p<0.001), more complicated (p=0.04), and had more septations (p=0.01) than in the follow-up group. The origin of the adnexal lesion was confirmed as the ovary in 59 (83%) patients, and as the peritoneum in 8 (11.2%) patients during surgery. All of the adnexal lesions arising after hysterectomy and required a re-operation were confirmed to be benign. Conclusion: Almost half of the lesions detected after hysterectomy disappeared during the follow-up period. The adnexal lesions that were re-operated were more symptomatic, larger, and had more complicated lesions. All lesions that were re-operated were found to be benign, mostly originating from the ovary.

Clomiphene Citrate Treatment Cycle Outcomes of Polycystic Ovary Syndrome Patients Based on Basal High Sensitive C-Reactive Protein Levels: A Cross-Sectional Study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is highly associated with an ovulatory infertility, features of the metabolic syndrome, including obesity, insulin resistance and dyslipidemia. Serum concentrations of high sensitive C-reactive protein (hs-CRP) were significantly higher in obese than in non-obese PCOS patients at baseline, suggesting a relationship between elevated hs-CRP levels and obesity. The aim of this study was to evaluate whether cycle day 3 hs-CRP levels before clomiphene citrate (CC) treatment would predict cycle outcomes in women with PCOS. MATERIALS AND METHODS: This cross-sectional study was conducted among 84 infertile women with PCOS who were treated with CC at Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara, Turkey, between January 2014 and January 2015. Based on the exclusion criteria, cycle outcomes of remaining 66 infertile women with PCOS treated with CC were analyzed. The hs-CRP levels and insulin resistance indexes were evaluated on day 3 of the CC treatment cycle. The primary outcome measures were number of preovulatory follicles measuring≥17 mm and pregnancy rates. RESULTS: The mean ± SD age of the patients was 24.0 ± 3.8 years (range 18-36). The mean ± SD body mass index (BMI) of the patients was 25.7 ± 4.9 (range 17-43). Fifty patients developed dominant follicle (75%) and 5 patients established clinical pregnancy during the study (clinical pregnancy rate: 7%). The mean ± SD baseline hs-CRP, fasting insulin and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) values of the patients with and without dominant follicle generation during treatment cycle were 6.42 ± 7.05 and 4.41 ± 2.95 (P=0.27), 11.61 ± 6.94 and 10.95 ± 5.65 (P=0.73), 2.68 ± 1.79 and 2.41 ± 1.30 (P=0.58), respectively. The mean ± SD baseline hs-CRP, fasting insulin and HOMA-IR values of the patients with and without clinical pregnancy establishment following treatment cycle were 6.30 ± 2.56 and 5.90 ± 6.57 (P=0.89), 11.60 ± 7.54 and 11.44 ± 6.61 (P=0.95), 2.42 ± 1.51 and 2.63 ± 1.70 (P=0.79), respectively. CONCLUSION: In this study, we did not observe a predictive value of cycle day 3 hs-CRP levels on preovulatory follicle development and pregnancy rates among infertile PCOS patients treated with CC. Also, no relationship between HOMA-IR values and dominant follicle generation or clinical pregnancy establishment was demonstrated in our study, confirming the previous studies emphasizing the neutral effect of metformin utilization before and/or during ovulation induction to pregnancy rates.

Evaluation of time lapse for establishing distal tubal occlusion diagnosis during hysterosalpingography procedure performed by using water soluble contrast media.

BACKGROUND: Hysterosalpingography (HSG) is the most frequently used diagnostic measure for simultaneously determining uterine abnormalities and tubal status among subfertile women. Despite several broader advantages such as availability and increased experience, the subjectivity involved during administration of the HSG procedure itself, and necessary imaging review, decreases the reliability and accuracy of HSG. In this study, we evaluated the time intervals between X-ray imaging during HSG procedure to establish the presence of distal tubal occlusion. METHODS: Our study evaluated the HSG records of 89 women who underwent diagnostic laparoscopy for infertility work-up. Patients who were diagnosed with distal tubal occlusion upon receiving HSG and patients who demonstrated tubal patency on HSG were included in the study, to compare the time intervals in seconds from the tubal visualization view to the last fluoroscopic X-ray shot during the HSG procedure with tubal patency on diagnostic laparoscopy. RESULTS: A statistically significant correlation regarding tubal patency between HSG procedures and diagnostic laparoscopy chromopertubation procedures was demonstrated. Although nearly statistically significant, the interval in seconds between the first HSG imaging and distal tubal filling was shorter for patients with patent tubes on diagnostic laparoscopy than patients with bilateral tubal occlusion (8.4±31.9 and 12.0±19.7, respectively; p=0.057). Time period intervals between the first and the last HSG, and between distal tubal filling to the last HSG of patients with patent tubes on diagnostic laparoscopy and patients with bilateral distal tubal occlusion were found to be statistically similar. CONCLUSION: Although a trend exists towards shorter time period intervals between the first uterine visualization and distal tubal filling graphy among patients with tubal patency, rather than patients with distal tubal occlusion confirmed by diagnostic laparoscopy, clinically reliable objective time period intervals for finalizing the HSG procedure and proceeding with diagnostic laparoscopy due to distal tubal occlusion diagnosis on HSG could not be detected.

Does intrauterine insemination timing matter for achieving pregnancy during ovulation induction using gonadotropins? A retrospective cohort study.

BACKGROUND: Intrauterine insemination (IUI) is a commonly used procedure to increase the infertile couples' chance of pregnancy. Single or double insemination and different timing choices are modifications of this intervention. The aim of this study was to elucidate the effect of the IUI procedure on clinical pregnancy rates when performed at 24 hours or 36 hours after ovulation triggered by human chorionic gonadotropin (hCG) following ovulation induction with gonadotropins. METHODS: One hundred and thirteen women diagnosed with polycystic ovarian syndrome (PCOS) (as per Rotterdam's criteria) or unexplained infertility, who were treated using gonadotropins for ovulation induction and IUI for increasing fertilization potential, were recruited from the medical records of the infertility clinic. Demographic features, cycle outcomes, and clinical pregnancy rates of the patients were compared based on two different timing strategies of IUI (24 hours and 36 hours) following ovulation trigger using hCG. RESULTS: Clinical pregnancy rates per cycle were 22.9% in the PCOS group and 26.9% in the unexplained group. The clinical pregnancy rates according to the timing of IUI were found to be similar for PCOS patients, unlike patients with unexplained infertility whose clinical pregnancy rates were significantly better when the IUI procedure was performed 24 hours following the hCG trigger. The cycle day of hCG trigger was also found to be significantly related to clinical pregnancy rate as utilizing a later hCG trigger day appeared to positively affect the odds of clinical pregnancy establishment. CONCLUSION: IUI performed at either 24 hours or 36 hours after ovulation triggered by hCG injection does not change clinical pregnancy rates for PCOS patients. Patients with unexplained infertility seem to benefit from earlier IUI procedures, which increases their fertility potential during ovulation induction with gonadotropins. Avoiding earlier than physiologically needed artificial-hCG triggering before IUI procedures results with better pregnancy rates.

Which is the best intrauterine insemination timing choice following exogenous hCG administration during ovulation induction by using clomiphene citrate treatment? A retrospective study.

OBJECTIVE: To evaluate the impact of intrauterine insemination timing performed 24 or 36 h later following ovulation trigger on clinical pregnancy rate during ovulation induction with clomiphene citrate among infertile women was the objective of this study. METHODS: The medical records of 280 infertile patients who have underwent ovulation induction by using clomiphene citrate have been evaluated and cycle outcomes of the patients have been investigated specifically based on the timing of intrauterine insemination during the treatment cycle. RESULTS: The clinical pregnancy rate of the study group based on the timing of intrauterine insemination (24 vs. 36 h following hCG trigger) was found to be similar regardless of infertility type. The cycle day of which hCG trigger has been performed was found to be significantly longer for patients who have achieved clinical pregnancy than patients who have not got pregnant following the treatment cycle. Dominant follicle diameter has not been found to affect clinical pregnancy rate during treatment cycles with clomiphene citrate. CONCLUSIONS: In this study, intrauterine insemination timing did not affect the cycle outcomes whether the procedure has been performed 24 or 36 h later following ovulation trigger with exogenous hCG utilization. The longer period of treatment cycle during ovulation induction with clomiphene citrate resulted with higher clinical pregnancy rate. Intrauterine insemination can be done successfully at either 24 or 36 h after hCG in clomiphene citrate stimulated cycles. This will allow more flexibility and convenience for both physicians and patients, especially during weekends.

Association between adverse perinatal outcomes and amino acid levels measured with nutrient questionnaire in adolescent pregnancies.

BACKGROUND: To evaluate the maternal serum amino acid levels in first trimester adolescent pregnancies by using a new developed dietary questionnaire. METHODS: A group of 169 pregnant women in the first trimester of their pregnancy were asked to complete the dietary questionnaire. Among all the women, 39 were adolescent pregnancies. The results of the questionnaire were evaluated by a nutrient database program (BeBiS software program) designed to evaluate Turkish traditional foods and commercial processed foods. RESULTS: There was no statistically significant difference between the groups in terms of body mass index and educational and socio-economic status. The mean age and gravidity was statistically significantly lower in adolescent pregnancies. The mean isoleucine, leucine, lysine, methionine, phenylalanine, tyrosine, threonine, valine, arginine, and proline levels were statistically significantly lower in adolescent pregnancies. Receiver operating characteristic (ROC) curve analysis showed the cut-off values of these amino acids. Of these amino acids; lower values of histidine, serine, and alanine were associated with lower birth weight, and lower values of histidine and alanine were associated with preterm delivery. CONCLUSION: To the best of our knowledge, this is the first study evaluating the amino acid levels in adolescent pregnancies. According to this study, some amino acid levels were lower in adolescent pregnancies and associated with adverse perinatal outcomes. Further studies with maternal and perinatal outcomes are needed to demonstrate the effects of these amino acids in such pregnancies.

The reproductive outcome of women with hypogonadotropic hypogonadism undergoing in vitro fertilization.

The aim of this study was to evaluate the reproductive outcome and assisted reproductive technology (ART) outcomes of patients with hypogonadotropic hypogonadism (HH) and to compare the results with male factor (MF) infertility patients. The reproductive outcome of 33 HH patients was evaluated retrospectively and compared with results of 47 patients with mild male factor infertility. For ovulation induction, human menopausal gonadotropin (hMG) was used in HH patients and recFSH was used in MF infertility patients. HH patients were divided into subgroups according to retrieved oocyte numbers and the groups were compared with each other. The main outcome measures were total gonadotropin dose used, duration of stimulation, human chorionic gonadotropin (hCG) day estradiol level and endometrial thickness, oocyte number retrieved, and rate of clinical pregnancy. ART outcomes and cycle characteristics of 33 HH patients were compared with 47 MF infertility patients. There was no difference in age and body mass index (BMI) between the groups, but mean follicle stimulating hormone FSH and luteinizing hormone LH levels were significantly lower in the HH group (p < 0.001). Duration of stimulation was 12.5 ± 2.06 days in the HH patients and 10.08 ± 1.62 days in the MF infertility patients and the difference was significant (p < 0.001). Total gonadotropin dose used was higher in the HH group than the MF infertility group (p < 0.001). However, there were no differences in hCG day estradiol levels, endometrial thickness on hCG day, total oocyte number retrieved, MII oocyte number, and pregnancy rate. In the HH subgroups, patient ages were significantly lower in the >15 oocyte retrieved group. Although patients with HH have a long-term estrogen deficiency, their response to controlled ovarian hyperstimulation treatment is similar to normal women. However, the HH group is heterogeneous and estimating the ovarian reserve before treatment is not always possible in this group.

Can serum estradiol levels on the fourth day of IVF/ICSI cycle predict outcome in poor responder women?

We aimed to investigate the value of fourth day serum estradiol levels in predicting cycle outcome in poor responders. The medical records of 426 patients with low oocyte yield following controlled ovarian hyperstimulation (COH) treatment for a procedure in our institution's center for ART between 2008 and 2013 were evaluated. Eighty-eight patients exhibiting poor ovarian response (POR) were included in the study. The clinical outcomes of IVF/ICSI were compared based on the basal hormone profile, clinical, and laboratory parameters. Cycle day 4 E2 levels below 110 pg/ml had an odds ratio of 6.05 (95% CI 2.33-15.7; p < 0.001) for embryo transfer. The early follicular response to ovarian stimulation can be anticipated with the cycle day 4 estradiol levels during COH. When a low day 4 serum estradiol level is encountered, abandoning the current COH and proceeding with agents that increase ovarian response to ovarian stimulation before the next treatment cycle can be a realistic approach.

Does the serum E2 level change following coasting treatment strategy to prevent ovarian hyperstimulation syndrome impact cycle outcomes during controlled ovarian hyperstimulation and in vitro fertilization procedure?

OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) remains as a clinical problem for hyperresponder patients during controlled ovarian hyperstimulation and in vitro fertilization (COH-IVF) procedure. Herein, we aimed to evaluate the COH-IVF outcomes in hyperresponder patients managed with coasting treatment strategy for OHSS prevention regarding the establishment of clinical pregnancy as an endpoint of the treatment cycle. MATERIALS AND METHODS: The medical records related to the COH-IVF outcome in 119 hyperresponder patients who have exhibited a serum estradiol level greater than or equal to 3000 pg/mL were evaluated. The study was conducted on a total of 119 patients, 98 of whom have been treated by coasting or coasting with GnRH antagonist co-treatment strategies, while the remaining 21 women (control group) have not been managed with coasting treatment. The COH and IVF-ET outcomes in the 119 patients were compared based on the coasting treatment situation. RESULTS: Among the women who received coasting treatment, the number of patients demonstrating E2 level decrement and also E2 level decrement rate after coasting were similar between patients with and without clinical pregnancy. Total gonadotropin dose, 2PN number, embryo number, and fertilization rate were significantly higher in the patients with a clinical pregnancy. CONCLUSION: The coasting treatment is a clinically useful preventive strategy for OHSS avoidance. GnRH antagonist co-treatment decreases the duration of coasting although any detrimental or ameliorating impact of this effect on pregnancy rates have not been seen. The E2 level decrement or increment following coasting treatment seems not to be related to cycle outcomes.

Hepcidin and erythropoietin measurements in the cord blood of neonates with meconium-stained amniotic fluid.

AIM: To compare hepcidin and erythropoietin levels in the cord blood of neonates with meconium-stained amniotic fluid (MSAF) to levels obtained from age-, body mass index- and gravidity-matched neonates with clear amniotic fluid. METHODS: A cross-sectional controlled study was conducted in secondary and tertiary care centers. Cord blood samples of 40 neonates following term gestations (≥37 weeks' gestation) with MSAF and 40 maternal age-, body mass index- and gravidity-matched controls with clear amniotic fluid were analyzed in this study. Demographic data, delivery outcomes and laboratory evaluations were recorded. RESULTS: Cord blood pH levels were lower in fetuses with MSAF when compared to those with clear amniotic fluid (P=0.0001). Fetuses with MSAF had higher cord blood erythropoietin levels in comparison to those with clear amniotic fluid (P=0.0001). Delivery outcomes and hepcidin measurements were similar in both groups. CONCLUSIONS: We demonstrated a significant relationship between erythropoietin levels and meconium passage, but failed to show the existence of a relationship between hepcidin levels and meconium passage.