Dual trigger with the combination of gonadotropin-releasing hormone agonist and standard dose of human chorionic gonadotropin improves in vitro fertilisation outcomes in poor ovarian responders.

The study aimed to evaluate the impact of the dual trigger with the combination of GnRH agonist and standard dose of recombinant hCG on IVF outcomes in poor ovarian responders with GnRH antagonist protocol. 1283 cycles of 1010 poor responder patients according to Bologna criteria were retrospectively analysed in terms of final oocyte maturation: dual trigger group (250 µg hCG + 0.2 mg triptorelin) or standard group (250 µg hCG). Primary outcome measures were the number of retrieved and mature oocytes. The secondary outcome measures were clinical pregnancy rates and live birth rates.The number of retrieved oocytes, mature oocytes, and the top-quality embryos transferred were significantly higher in the dual trigger group (p < .001). Fertilisation rates (73.6% vs 69.6%, p = .009), implantation rates (18.7% vs 14.6, p = .039), clinical pregnancy rate per embryo transfer (27.5% vs. 19.9%, p = .010) and live birth rate per embryo transfer (21.6% vs. 14.9%, p = .011) were also significantly higher in the dual trigger group as compared to the hCG trigger group. The usage of dual trigger with a GnRH agonist and a standard dosage of hCG could improve clinical pregnancy rates and live birth rates in poor ovarian responders undergoing GnRH antagonist IVF/ICSI cycles.IMPACT STATEMENTWhat is already known on this subject? Dual trigger with standard dose of hCG has been the subject of trials in normal responders to optimise IVF outcomes. The results of these studies showed significant improvements in implantation and pregnancy rates with an increase in the number of mature oocytes retrieved. As a result, dual trigger has become a popular ovulation trigger option in GnRH antagonist cycles.What do the results of this study add? There is limited data about the use of dual trigger in poor ovarian responders (PORs). According to our study, increasing the number of retrieved oocytes, mature oocytes, the number of fertilised oocytes, the number of transferred embryos and top quality embryos transferred by using dual trigger in patients with PORs have a positive impact on pregnancy outcomes.What are the implications of these findings for clinical practice and/or further research? These findings implies potential advantages of dual trigger usage for improving IVF outcomes in PORs. With large sample sized prospective randomised trials, dual trigger with combination of GnRHa and a standard dose of hCG might replace the traditional ovulation trigger with hCG in PORs.

The impact of the modified speculum application technique on the success rates of intrauterine insemination: A randomized controlled study.

OBJECTIVE: Intrauterine insemination (IUI) is frequently used to treat patients with ovulation disorders, cervical factor, mild male infertility and unexplained infertility. The aim of this study was to investigate the impact of modified speculum application on the success of IUI in patients with unexplained infertility. MATERIALS AND METHODS: This prospective randomized study reviewed 219 women who had undergone controlled ovarian hyperstimulation (COH)-IUI treatment. In the modified speculum application group (109 patients with 124 cycles), the screw of the vaginal speculum was loosened after passing the internal os with catheter and the vaginal speculum remained in this position to ensure closure of the cervix during the procedure. In the conventional speculum application group (110 patients with 132 cycles), the screw of the vaginal speculum was not loosened to close the lips of cervix after passing the internal os with the catheter and the vaginal speculum was removed after withdrawal of the insemination catheter. The primary outcome was live birth rate. RESULTS: The modified and conventional speculum application groups had statistically similar demographic and clinical characteristics. There were no significant differences between the study and the control groups in terms of the clinical pregnancy rate per cycle and per patient (24.1% vs 18.9% and 26.6% vs 22.7%, respectively), as well as the live birth rate per cycle and per patient (19.3% vs 15.1% and 22% vs 18.1% respectively). CONCLUSION: Applying gentle mechanical pressure on the portio vaginalis of the cervix using a vaginal speculum during IUI does not improve pregnancy and live birth rates in patients with unexplained infertility.

Serum vitamin D concentrations in young Turkish women with primary dysmenorrhea: A randomized controlled study.

OBJECTIVE: This study aims to investigate the possible role of vitamin D deficiency in primary dysmenorrhea by assessing serum 25-hydroxyvitamin D3 levels in a cohort which includes young Turkish women with primary dysmenorrhea and healthy controls. MATERIALS AND METHODS: A total of 683 women who were aged between 18 and 25 years and who were consecutively admitted to the study center were eligible. After the exclusion of 55 women, 184 women with primary dysmenorrhea were randomly assigned into the dysmenorrhea group and 184 women without dysmenorrhea were randomly allocated into the control group. RESULTS: The dysmenorrhea group had significantly less consumption of dairy products (p = 0.001), lower serum calcium (p = 0.001), lower serum vitamin D (p = 0.001) and higher serum parathyroid hormone (p = 0.001) than those of the control group. Hyperparathyroidism was significantly less frequent whereas vitamin D deficiency was significantly more frequent in the dysmenorrhea group (p = 0.001 for each). The dysmenorrhea patients with vitamin D deficiency had significantly higher visual analogue scale (VAS) scores (p = 0.001). Depression, irritability, mood swings, fatigue, headache and breast tenderness were significantly more frequent in the vitamin D deficiency group (p < 0.05 for all). The VAS scores of the dysmenorrhea patients correlated positively and significantly with serum parathyroid hormone levels (r = 0.666, p = 0.001) whereas these VAS scores correlated negatively and significantly with serum vitamin D levels (r = -0.713, p = 0.001). DISCUSSION: The significant and positive correlation between vitamin D levels and VAS scores and the significant reduction in serum vitamin D levels of the dysmenorrhea patients designate the possible role of vitamin D deficiency in the primary dysmenorrhea.

Elevated basal progesterone levels are associated with increased preovulatory progesterone rise but not with higher pregnancy rates in ICSI cycles with GnRH antagonists.

OBJECTIVE: To ascertain the association between basal progesterone (P) levels and the occurrence of preovulatory progesterone rise (PPR) and clinical pregnancy rates (CPRs) in ICSI cycles with GnRH antagonists. STUDY DESIGN: Serum P levels of 464 patients were measured on day 2 and day of hCG of cycles. Cycles with basal P levels>1.6ng/mL were cancelled. All embryos were cryopreserved in cycles with P levels≥2ng/mL on the day of hCG. The primary outcome measures were the incidence of PPR (P>1.5ng/mL) and CPR with regard to basal P. RESULTS: Basal P levels were significantly higher in cycles with PPR than in those without PPR (0.63±0.31 vs. 0.48±0.28ng/mL). Area under the curve for basal P according to ROC analysis to discriminate between elevated and normal P levels on the day of hCG was 0.65 (0.58-0.71 95% CI, p<0.01). The cut-off value for basal P levels that best discriminates between cycles with and without PPR was 0.65ng/mL. Cycles with basal P levels above 0.65ng/mL had a significantly higher incidence of PPR (30.9% vs. 13.5%) but similar clinical and cumulative pregnancy rates (38.8% vs. 31.1% and 41.7% vs. 32.6%, respectively) in comparison to cycles with basal P levels below 0.65ng/mL. In multivariate regression analysis, basal P levels, LH level on the first day of antagonist administration, and estradiol levels on the day of hCG trigger were the variables that predicted PPR. CONCLUSION: Basal P levels were associated with increased incidence of PPR but not with CPR.

Comparison of the standard GnRH antagonist protocol and the luteal phase estradiol/GnRH antagonist priming protocol in poor ovarian responders.

BACKGROUND/AIM: The aim of the study was to compare the luteal estradiol patch/GnRH antagonists priming protocol (LPP) with the standard GnRH antagonist protocol in poor ovarian responders (PORs) in terms of the outcomes of in vitro fertilization (IVF) treatment. MATERIALS AND METHODS: IVF outcomes of 265 cycles in 265 patients (106 in the LPP group, 159 in the standard GnRH antagonist group) were evaluated retrospectively. RESULTS: Mean length of stimulation (11.4 ± 2.7 vs. 10.0 ± 2.7 days; P < 0.05) and the total gonadotropin dose (3403 ± 1060 vs. 2984 ± 1112) used were significantly greater in the LPP group than in the standard GnRH antagonist protocol group. The mean number of oocytes retrieved (3.5 ± 2.6 vs. 3.7 ± 2.8), the number of mature oocytes (2.8 ± 2.2 vs. 2.6 ± 2.2), fertilization rates (65% vs. 62%), the number of embryos transferred (1.6 ± 0.6 vs. 1.7 ± 0.6), and implantation rates (16% vs. 13%) were similar. The cancellation rate did not significantly differ between the groups (9.4% vs. 13.2%). There were no significant differences in the clinical pregnancy (11.3% vs. 13.2%) or live birth rates per patient (3.8% vs. 9.4%) and clinical pregnancy (18.8% vs. 22.6%) or live birth rates per embryo transfer (6.3% vs. 12.9%) between the groups. CONCLUSION: LPP does not improve IVF outcomes when compared with the standard GnRH antagonist protocol in PORs.

Two cases of first onset intrahepatic cholestasis of pregnancy associated with moderate ovarian hyperstimulation syndrome after IVF treatment and review of the literature.

Intrahepatic cholestasis of pregnancy (ICP) is an uncommon disorder, which generally occurs in the second and third trimester of pregnancy with symptoms of pruritus. The cause of ICP is unknown but genetic, hormonal and environmental factors contribute to its pathogenesis. The aetiology of ICP is unclear but elevation in oestrogen levels thought to cause ICP is typically seen in the third trimester of pregnancy, and for this reason it is not usually considered in the differential diagnosis of pruritus and liver function disorders in the first trimester of the pregnancy. We present two cases of pregnancy after IVF treatment diagnosed with ICP following the development of OHSS, deteriorating liver function tests and severe pruritus.

Comparison of age-related changes in anti-Müllerian hormone levels and other ovarian reserve tests between healthy fertile and infertile population.

In this study, we aimed to determine whether anti-Müllerian hormone (AMH) levels vary between fertile and infertile populations and compare them with basal follicle-stimulating hormone (FSH) levels and antral follicle count (AFC). This was a prospective study that included 177 primarily infertile patients who underwent IVF treatment and 162 healthy fertile patients admitted to our clinic for benign diseases. FSH and AMH levels and the AFC of the infertile and fertile populations were compared between the age categories <30, 30-39 and ≥40. Correlations between AMH, basal FSH, and AFC with age were evaluated. AFC and AMH levels did not differ between the fertile and infertile groups in all age categories. AMH was inversely correlated with age in both the fertile and infertile populations. However, AFC revealed a stronger correlation with age in both the fertile and infertile populations compared with basal FSH and AMH. Age was positively correlated with basal FSH and inversely correlated with AMH and AFC. In conclusion, there was no significant difference between the fertile and infertile populations in terms of AMH or AFC. The decrease in ovarian reserve in infertile patients is directly related to age, not infertility.

Advanced oxidation protein products and malondialdehyde - the new biological markers of oxidative stress - are elevated in postmenopausal women.

OBJECTIVES: The aim of the study was to measure advanced oxidation protein products (AOPPs) as markers for oxidative stress to evaluate cardiovascular risk in pre- and postmenopausal women and to compare the results with malondialde-hyde (MDA) levels. MATERIAL AND METHODS: Twenty premenopausal women and 84 naturally postmenopausal patients were enrolled in the study. AOPP and MDA plasma levels were measured. The postmenopausal group was further subdivided into two groups: postmenopausal age of 40-49 and of 50-59 years. AOPP and MDA levels were compared between premenopausal, 40-49 and 50-59 year old menopausal women. RESULTS: Plasma AOPP and MDA levels in postmenopausal women were increased when compared with their premeno-pausal peers (123.83 ± 55.51 µmol/L vs. 61.59 ± 16.42 µmol/L and 6.50 ± 1.05 µmol/L vs. 5.98 ± 0.77 µmol/L; respectively). Mean plasma AOPP levels in the two menopausal age groups were both significantly higher from the premenopausal group (118.64 ± 59.1 µmol/L vs. 61.59 ± 16.42 µmol/L and 132.31 ± 48.97 µmol/L vs. 61.59 ± 16.42 µmol/L; respectively). No significant difference was found in mean AOPP levels between postmenopausal subjects of 40-49 and 50-59 years age (118.64 ± 59.12 µmol/L vs. 132.31 ± 48.97 µmol/L). Mean plasma MDA levels of each of two postmenopausal age groups were both significantly higher from the premenopausal group (6.50 ± 1.04 µmol/L vs. 5.98 ± 0.77 µmol/L and 6.50 ± 1.10 µmol/L vs. 5.98 ± 0.77 µmol/L; respectively). However, no statistically significant difference between the two postmenopausal age groups (6.50 ± 1.04 µmol/L vs. 6.50 ± 1.10 µmol/L) was found. CONCLUSIONS: AOPP and MDA levels are elevated in postmenopausal women as compared to their premenopausal peers, suggesting they can be used as markers for cardiovascular risk in postmenopausal women.

The impact of premature progesterone rise on the outcome of intrauterine insemination cycles with controlled ovarian hyperstimulation in unexplained infertility.

OBJECTIVE: To ascertain the incidence of premature progesterone P rise and its impact on outcomes in controlled ovarian hyperstimulation and intrauterine insemination (COH-IUI) cycles, and also to identify variables related with premature P rise. STUDY DESIGN: Four hundred sixty cycles of 460 couples with unexplained infertility having COH-IUI treatment with a starting dose of 75IU recombinant FSH enrolled in this prospective study. Serum P levels were determined on the day of hCG trigger. Premature P rise was defined as progesterone ≥1ng/mL. The primary outcome measure was live birth per cycle with regard to P levels of ≥1ng/mL and ≥1.5ng/mL. Secondary outcome measures were cycle characteristics associated with P rise. RESULTS: The incidence of premature P rise was 22.0%. P levels on hCG day were significantly lower in cycles with live birth as compared to cycles without live birth 0.49±0.51 vs. 0.73±0.82ng/mL. Live birth rates were significantly lower in cycles with hCG day P levels ≥1.0ng/mL (%7.9 vs. %22.6) and ≥1.5ng/mL (%6.4 vs. %20.8). Among age, number of dominant follicles, estradiol, LH and P levels on the day of hCG trigger, it was found that P levels was the only significant variable to predict live birth on multivariate analysis. The number of dominant follicles on hCG day and premature LH surge were the only significant variables related with premature P rise. CONCLUSION: Premature P is a frequent feature of COH-IUI cycles and associated with decreased live birth rates.

Recombinant FSH increases live birth rates as compared to clomiphene citrate in intrauterine insemination cycles in couples with subfertility: a prospective randomized study.

OBJECTIVE: To compare the efficacy of intrauterine insemination (IUI) cycles undergoing ovarian hyperstimulation with recombinant FSH (rFSH) or clomiphene citrate (CC) in couples with unexplained and male subfertility. STUDY DESIGN: Two hundred and nineteen subfertile couples were enrolled in this randomized prospective study. Patients were randomly assigned to receive 75IU rFSH or 100mg CC for two cycles. Cycles with more than four dominant follicles and/or serum E2 levels higher than 1500pg/ml were cancelled. Primary outcomes were live birth rates per patient and per cycle, secondary outcomes were clinical and multiple pregnancy rates. RESULTS: One hundred and nine women received rFSH and 110 received CC. Both cumulative clinical pregnancy and live birth rates per patient were significantly higher in gonadotropin group (43.1% and 37.6%) as compared to CC group (28.2% and 20%) (p<0.05 and p<0.01, respectively). Live birth rate per cycle were significantly higher in gonadotropin group (24.3%) in comparison with CC group (13.8%) (p<0.05). However, clinical pregnancy rate per cycle was not different between groups (28.4% vs 20%) (p>0.05). There was no significant difference between gonadotropin and CC group groups in terms of multiple pregnancy rates (10.4% vs 12.5%, p>0.05). Continuous variables were compared with Student's t test. Categorical variables were compared with Chi square test. CONCLUSION: rFSH has significantly higher cumulative clinical pregnancy and live birth rates when compared to CC with similar multiple pregnancy rates in subfertile patients undergoing IUI.

Effects of anticoagulant therapy on pregnancy outcomes in patients with thrombophilia and previous poor obstetric history.

This study investigates the effects of anticoagulant therapy on pregnancy outcomes in 204 patients with thrombophilia and previous poor obstetric outcomes. Patients with poor obstetric history (pre-eclampsia, intrauterine growth retardation, fetal death, placental abruption, recurrent pregnancy loss) and having hereditary thrombophilia were included in this study. Poor obstetric outcomes were observed more frequently in patients who had not taken anticogulant therapy compared with treated group. Live birth rate, gestational age at birth and Apgar scores were significantly higher in the treated group when compared with the untreated group. There were no significant differences in terms of birthweight, mode of delivery and admission rates to the neonatal intensive care unit (NICU). Low-molecular-weight heparin (LMWH) plus acetylsalicylic acid (ASA) had higher gestational age at birth, Apgar scores, live birth rate and a lower abortion rates when compared with controls; in contrast, no significant difference was observed in terms of birthweight, mode of delivery, obstetric complications and admission rates to NICU. There were no significant differences between control group and both LMWH only and ASA only groups in terms of gestational age at birth, Apgar scores, birthweight, mode of delivery, obstetric complications and admission rates to NICU. Only LMWH group had higher live birth rate as compared with control group. The use of only ASA did not seem to affect the perinatal complication rates and outcomes. In conclusion, anticoagulant therapy with both LMWH and ASA seems to provide better obstetric outcomes in pregnant women with thrombophilia and previous poor obstetric outcomes.

Can uterine artery Doppler parameters predict copper intrauterine device-induced side effects?

OBJECTIVES To evaluate the predictive value of uterine artery Doppler characteristics in predicting copper intrauterine device (IUD)-induced side effects such as dysmenorrhoea and menorrhagia, and worsening of dyspareunia. METHODS One hundred and twenty regularly menstruating women were enrolled in the study. All underwent transvaginal uterine artery Doppler analysis in the early follicular phase, on two occasions: before insertion of the IUD, and six months after insertion. Pre- and post-insertion resistance (RI) and pulsatility (PI) indices of the uterine arteries were measured. Doppler parameters were compared between subjects experiencing an increase in IUD-mediated side effects and those reporting no change. RESULTs RI and PI of all participants before and after IUD insertion were not significantly different (0.75 ± 0.06 vs. 0.74 ± 0.09, p = 0.49; 1.81 ± 0.55 vs. 1.83 ± 0.70, p = 0.7, respectively). No significant difference was found in the comparison of pre- and post-insertion PI and RI values of women who had increased- and those who experienced no change in dysmenorrhoea, dyspareunia and duration/amount of menstruation. CONCLUSIONS No major changes in uterine blood flow were observed in women experiencing increased menstrual bleeding, dyspareunia or dysmenorrhoea after insertion of a copper IUD. The occurrence of these effects cannot be predicted by prior Doppler flow analysis.

Antral follicle count determines poor ovarian response better than anti-Müllerian hormone but age is the only predictor for live birth in in vitro fertilization cycles.

PURPOSE: To determine the predictive value of serum anti-müllerian hormone (AMH) concentrations and antral follicle counts (AFC), on ovarian response and live birth rates after IVF and compare with age and basal FSH. METHODS: Basal levels of AMH, FSH and antral follicle count were measured in 192 patients prior to IVF treatment. The predictive value of these parameters were evaluated in terms of retrieved oocyte number and live birth rates. RESULTS: Poor responders in IVF were older, had lower AFC and AMH but higher basal FSH levels. In multivariate analysis AFC was the best and only independent parameter among other parameters and AMH was better than age and basal FSH to predict poor response to ovarian stimulation. Addition of AMH, basal FSH, age and total gonadotropin dose to AFC did not improve its prognostic reliability. Area under curve (AUC) for each parameter according to ROC analysis also revealed that AFC performed better in poor response prediction compared with AMH, basal FSH and age. The cut-off point for mean AMH and AFC in discriminating the best between poor and normal ovarian response cycles was 0.94 ng/mL (with a sensitivity of 70% and a specificity of 86%) and 5.5 (with a sensitivity of 91% and a specificity of 91%), respectively. However, age was the only independent predictor of live birth in IVF as compared to hormonal and ultrasound indices of ovarian reserve. CONCLUSION: AFC is better than AMH to predict poor ovarian response. Although AMH and AFC could be used to predict ovarian response they had limited value in live birth prediction. The only significant predictor of the probability of achieving a live birth was age.