Importance of IGF-I levels in IVF: potential relevance for growth hormone (GH) supplementation

PurposeGrowth hormone (GH) supplementation in association with in vitro fertilization (IVF) is worldwide again increasing, even though study outcomes have been discrepant. Since GH acts via insulin-like growth factor-1 (IGF-1), its utilization in IVF would only seem to make sense with low IGF-1. We, therefore, determined whether IGF-I levels affect IVF outcomes.MethodsRetrospectively, 302 consecutive first fresh, non-donor IVF cycles were studied, excluding patients on GH supplementation. Patients were divided into 3 subgroups: IGF-1 in lower 25th percentile (group A, < 132 ng/mL, n = 64); 25th–75th percentile (B, 133–202 ng/mL, n = 164), and upper 25th percentile (C, > 202 ng/mL, n = 74). IGF-1 was tested immunochemiluminometric with normal range at 78–270 ng/mL. Because of the study patients’ adverse selection and low pregnancy chances, the main outcome measure for the study was cycle cancellation. Secondary outcomes were oocyte numbers, embryos transferred, pregnancies, and live births.ResultsGroup A was significantly older than B and C (P = 0.019). IGF-1 decreased with increasing age per year by 2.2 ± 0.65 ng/mL (P = 0.0007). FSH was best in group B and worst in A (trend, P = 0.085); AMH was best in B and worst in A (N.S.). Cycle cancellations were lowest in C (11.6%) and highest in A (25.0%; P = 0.042). This significance further improved with age adjustment (P = 0.021). Oocytes, embryo numbers, pregnancies, and live birth rates did not differ, though oocyte numbers trended highest in B.ConclusionsHere presented results support the hypothesis that IGF-1 levels affect IVF outcomes. GH treatments, therefore, may be effective only with low IGF-1.     

The effect of ICSI in infertility couples with non-male factor: a systematic review and meta-analysis

PurposeWe performed a systematic review and meta-analysis of available literature to investigate the efficacy of the intracytoplasmic sperm injection (ICSI) in couples with non-male factor with respect to the clinical outcomes.MethodsThe literature search was based on EMBASE, PubMed, and the Cochrane Library. All studies published after 1992 until February 2020 and written in English addressing patients in the presence of normal semen parameters subjected to ICSI and in vitro fertilization (IVF) were eligible. Reference lists of retrieved articles were hand-searched for additional studies. The primary outcomes were fertilization rate, clinical pregnancy rate, and implantation rate; the secondary outcomes were good-quality embryo rate, miscarriage rate, and live birth rate.ResultsFour RCTs and twenty-two cohort studies fulfilling the inclusion criteria were included. Collectively, a meta-analysis of the outcomes in RCTs showed that compared to IVF, ICSI has no obvious advantage in fertilization rate (RR = 1.16, 95% CI: 0.83–1.62), clinical pregnancy rate (RR = 1.04, 95% CI: 0.66–1.64), implantation rate (RR = 1.12, 95% CI: 0.67–1.86), and live birth rate (RR = 1.17, 95% CI: 0.43–3.15). Pooled results of cohort studies demonstrated a statistically significant higher fertilization rate (RR = 1.16, 95% CI: 1.03–1.31) and miscarriage rate (RR = 1.04, 95% CI: 1.01–1.06) in the ICSI group; furthermore, higher clinical pregnancy rate (RR = 0.85, 95% CI: 0.77–0.94), implantation rate (RR = 0.78, 95% CI: 0.65–0.95), and live birth rate (RR = 0.86, 95% CI: 0.79–0.94) was founded in the IVF group; no statistically significant difference was observed in good-quality embryo rate (RR = 0.98, 95% CI: 0.93–1.04).ConclusionICSI has no obvious advantage in patients with normal semen parameters. Enough information is still not available to prove the efficacy of ICSI in couples with non-male factor infertility comparing to IVF.Electronic supplementary materialThe online version of this article (10.1007/s10815-020-01970-9) contains supplementary material, which is available to authorized users.     

Assessment of density gradient centrifugation (DGC) and sperm chromatin dispersion (SCD) measurements in couples with male factor infertility undergoing ICSI

Purpose

To investigate how effectively density gradient centrifugation (DGC) improves sperm nuclear integrity and to determine whether the sperm chromatin dispersion (SCD) test of sperm nuclear integrity in native or DGC-treated semen can predict the outcome of assisted reproductive technology (ART) in couples undergoing intracytoplasmic sperm injection (ICSI).

Methods

The DNA integrity of spermatozoa from 63 male factor infertility patients undergoing ICSI was analyzed by the SCD test before and after DGC. The predictive value of the sperm DNA fragmentation index (DFI) for ART outcomes was assessed in a cohort of 45 patients who were undergoing fresh embryo transfer. For the analysis, they were divided into pregnant and non-pregnant groups and, independently, into high sperm DFI (DFI > 30 %) and low sperm DFI (DFI ≤ 30 %) groups. Both raw and DGC semen parameters were examined.

Results

In the asthenospermia and oligozoospermia groups, DGC decreased the sperm DFI from 31.5 ± 19.7 and 28.5 ± 10.3 to 19.2 ± 18.3 and 16.0 ± 12.8, respectively (P < 0.01). DGC decreased the sperm DFI in the severe oligozoospermia group from 41.4 ± 19.0 to 36.3 ± 20.6 (P > 0.01). The pregnant and non-pregnant groups did not differ in their fertilization rate and sperm DFI in native or DGC semen (P > 0.05). There was also no significant difference between the high sperm DFI (DFI > 30 %) and low sperm DFI (DFI ≤ 30 %) groups with regard to fertilization rate, implantation rate, and clinical pregnancy rate for both native and DGC semen (P > 0.05). The patients undergoing ICSI with a high sperm DFI had a higher pregnancy loss rate (defined as spontaneous miscarriage or biochemical pregnancy) compared with patients with a low sperm DFI in both the native and DGC semen groups.

Conclusions

DGC highly significantly reduces sperm DNA fragmentation in the semen of ICSI patients, with the exception of those with severe oligozoospermia. The results of the SCD test of sperm DNA fragmentation in native or DGC semen do not correlate with the fertilization rate, implantation rate, or clinical pregnancy rate in patients undergoing ICSI.     

Ratio of progesterone-to-number of follicles as a prognostic tool for in vitro fertilization cycles

Purpose

To establish a ratio of the P level to the number of follicles (P/F ratio) on the day of human chorionic gonadotropin (hCG) administration and to evaluate whether this ratio is associated with in vitro fertilization (IVF) outcome.

Methods

This study was conducted between January 2012 and June 2013. A total of 337 patients with cleavage-stage day-3 fresh embryo transfer with P levels ≤1.5 ng/mL on the day of hCG administration were included in the study. The main outcome was ongoing pregnancy rate.

Result(s)

The P/F ratio was calculated according to the equation (P[ng/mL]/number of follicles) on the day of final oocyte maturation. Using ROC, we established a cut-off level of 0.075 for the P/F ratio. The area under the curve (AUC) (0.756; 95 % confidence interval [CI]: 0.704–0.807) indicated that it was a good prognostic test. In group 1 (patients under 36 years old), the ongoing pregnancy rates were 57 and 30 % for patients with P/F ratios ≤ .075 and > .075, respectively, (p = 0.003). In group 2 (patients between 36 and 39 years old), the ongoing pregnancy rates were 58 % and 17 % (p = 0.001) for patients with P/F ratios ≤ .075 and > .075, respectively. In group 3 (patients ≥ 40 years old), the ongoing pregnancy rates were 41.7 and 10.9 % (p = 0.001) for patients with P/F ratios ≤ .075 and > .075, respectively.

Conclusions

The P/F ratio is a good prognostic test for predicting IVF outcome that can correlate the P level with ovarian response.     

Single nucleotide polymorphisms in the Anti-Müllerian hormone (AMH Ile49Ser) and Anti-Müllerian hormone type II receptor (AMHRII −482 A>G) as genetic markers in assisted reproduction technology

PurposeThe aim of the study was to evaluate whether the presence Antimullerian hormone (AMH) and Antimullerian hormone type II receptor (AMHRII) single nucleotide polymorphisms (SNPs) Ile⁴⁹Ser and -482A>G respectively are related to the assisted reproduction outcome.MethodsA prospective cross-sectional observational study was conducted in order to assess the distribution of AMH and AMHRII SNPs in two cohorts, one of healthy women (N = 100) and the control group and the IVF/ICSI group (N = 151) consisted of women undergoing IVF/ICSI treatment for infertility. Furthermore, a prospective longitudinal observational study was performed on the latter group to assess possible associations of these SNPs with patients’ characteristics and controlled ovarian stimulation (COS) and pregnancy outcome.ResultsAmong non-carriers of the AMH (Ile⁴⁹Ser) polymorphism, basal FSH levels were lower in those with more than two of previous IVF attempts and fertilization rate was statistically higher in those with peak serum E2 levels below 1500 pg/ml, whereas among non-carriers of the AMHRII (−482 A>G) polymorphism, number of follicles was higher in those with more than two previous IVF attempts and total dose of gonadotropins was lower in those with peak serum E2 levels above 1500 pg/ml.ConclusionsThere was evidence that in specific subgroups of women undergoing IVF/ICSI, AMH and AMHRII SNPs may be related to patients’ characteristics and controlled ovarian stimulation and pregnancy outcome and thus may provide a means for the prediction of ovarian response in specific subgroups of women entering an IVF/ICSI program.     

Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles

Purpose

To investigate the impact of elevated serum estradiol (E₂) levels on the day of hCG trigger on the birth weight of term singletons after fresh In Vitro Fertilization (IVF)-Embryo Transfer (ET) cycles.

Methods

Retrospective cohort study of all patients initiating fresh IVF-ET cycles resulting in live births between January 2004 and February 2013. The incidence of low birthweight (LBW) term singletons in patients with E₂ levels on day of hCG trigger above or below the 95 % cutoff for E₂ values in our clinic (3,069.2 pg/mL) was estimated. Multiple gestations and vanishing twin pregnancies were excluded.

Results

Two thousand nine hundred thirty-nine singleton live births were identified for inclusion. One hundred forty seven (5 %) and 2792 (95 %) live singleton births occurred in patients with peak E₂ levels above and below 3,069.2 pg/mL, respectively. The overall incidence of term LBW was 5.4 % in the >3,069.2 pg/mL group compared to 2.4 % in the ≤3,069.2 pg/mL group (P = .038). An E₂ level >3,069.2 pg/mL on the day of hCG administration was associated with increased odds of LBW term singletons (OR = 2.29; 95 % CI = 1.03–5.11). The increased odds remained unchanged when adjusting for maternal age (aOR = 2.29; 95 % CI = 1.02–5.14; P = .037), gestational age at delivery (aOR = 2.04; 95 % CI = 1.22–3.98; P = .025), and day 3 versus blastocyst transfer (aOR = 2.5; 95 % CI = 1.11–5.64; P = .023).

Conclusions

Peak E₂ level >3,069.2 pg/mL is associated with increased odds of LBW term singletons after fresh IVF-ET cycles. Conservative stimulation protocols aiming not to exceed an E₂ level of 3,000 pg/mL may be advantageous for placentation and fetal growth if a fresh transfer is planned.     

Aging attenuates the ovarian circadian rhythm

ObjectiveTo study the effect of aging on ovarian circadian rhythm.DesignHuman and animal study.SettingUniversity hospital and research laboratory.Patients/animalsHuman granulosa cells were obtained by follicular aspiration from women undergoing in vitro fertilization (IVF), and ovarian and liver tissues were obtained from female C57BL/6 mice.Intervention(s)None.Main outcome measure(s)Expression of circadian genes in young and older human granulosa cells and circadian rhythm in ovaries and livers of young and older mice.Result(s)All examined circadian clock genes in human granulosa cells showed a downward trend in expression with aging, and their mRNA expression levels were negatively correlated with age (P < 0.05). Older patients (≥ 40 years of age) had significantly reduced serum anti-Müllerian hormone (AMH) levels. Except for Rev-erbα, all other examined circadian clock genes were positively correlated with the level of AMH (P < 0.05). The circadian rhythm in the ovaries of older mice (8 months) was changed significantly relative to that in ovaries of young mice (12 weeks), although the circadian rhythm in the livers of older mice was basically consistent with that of young mice.Conclusion(s)Lower ovarian reserve in older women is partially due to ovarian circadian dysrhythmia as a result of aging.Electronic supplementary materialThe online version of this article (10.1007/s10815-020-01943-y) contains supplementary material, which is available to authorized users.     

New Innovation: Use of Flash Glucose Monitoring for Evaluating Glycaemic Variability,Patient Satisfaction and Clinical Utility in Pregnant Women with Diabetes

AimApplication of Flash glucose monitoring (FGM) system to evaluate glycaemic variability (GV), patient satisfaction and clinical utility in pregnant women with diabetes.MethodsThis prospective study was conducted in a tertiary care teaching hospital on 70 pregnant women with diabetes where blood sugar levels were monitored by FGM and self-monitoring of blood glucose (SMBG).ResultsFGM generated 19,950 readings versus 1470 readings by SMBG over 3 days. Glucose values measured by FGM and SMBG had significant positive correlation (r > 0.89; p < 0.001). Significant difference (p < 0.001) was present between minimum glucose values by FGM (52.49 ± 15.42 mg/dl) and SMBG (72.74 ± 18.30 mg/dl). FGM (20.9%) was able to pick exact duration of hypoglycaemia, while one-third of this duration was missed by conventional SMBG (14.7%; p < 0.05). Hypoglycaemic episodes were observed in 92.9% women by FGM as compared to 45.7% by SMBG (p < 0.001). No significant difference was observed in maximum glucose level or duration of hyperglycaemia by both methods. FGM identified hyperglycaemia in 74% women vs. 52% by SMBG (p < 0.001). GV calculated by using MODD by FGM was 118.4 ± 52.4 mg/dl and by SMBG was 83.2 ± 53.2 mg/dl (p < 0.001). 100% women preferred AGP vs. SMBG.ConclusionThis is the first study to evaluate FGM for GV and patient satisfaction in women with GDM. Significant correlation was observed in glucose values by FGM and SMBG. FGM was more sensitive in detecting GV and hypoglycaemic excursions as compared to SMBG. All women preferred FGM over SMBG. Use of FGM gave new insights in clinical management of challenging cases.     

Comparison of in vitro fertilisation/intracytoplasmic sperm injection on live birth rates in couples with non-male factor infertility and advanced maternal age

PurposeTo determine if the use of ICSI in women of advanced maternal age with non-male factor infertility increases chances of live birth.MethodsRetrospective data analysis of 10 years of cycle data from a single Australian IVF clinic (Repromed). First cycle patients only of an advanced maternal age (≥ 35 years) with non-male factor infertility utilising standard IVF or ICSI insemination and having at least three oocytes collected at egg pick up were assessed for live birth following transfer of single genetically unscreened blastocyst (N = 577). Subanalysis of clinical pregnancy, miscarriage, fertilisation, embryo utilisation rate and having a blastocyst for transfer were considered. Unadjusted, covariate adjusted and propensity score weighted analysis were performed.ResultsThe use of standard IVF insemination in women ≥ 35 years with non-male factor infertility increased the chance of a live birth compared with ICSI insemination (unadjusted OR = 2.72, 95% CI [1.78, 4.17]; adjusted OR = 2.64, 95% CI [1.64, 4.27] and weighted OR = 2.26, 95% CI [1.72, 2.98] 31% vs 14%). All other outcomes (fertilisation rate, embryo utilisation, blastocyst for embryo transfer and miscarriage rate) were unaffected.ConclusionIn couples with advanced maternal age and non-male factor infertility, standard IVF insemination appears to increase the chance of a live birth compared with ICSI. As such, the results of this study support the use of routine IVF as the preferred insemination technique for older women in non-male factor infertility. However, future randomised controlled trials are still required to assess this policy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10815-020-02026-8.     

Detection of early placental hormone production in embryo transfer cycles lacking a corpus luteum

PurposeThis study sought to identify the initiation of placental hormonal production as defined by the production of endogenous estradiol (E2) and progesterone (P4) in a cohort of patients undergoing programmed endometrial preparation cycles with single embryo transfers resulting in live-born singletons.MethodsIn this retrospective cohort study, patients undergoing either programmed frozen-thawed embryo transfer (FET) with autologous oocytes or donor egg recipient (DER) cycles with fresh embryos were screened for inclusion. Only patients who underwent a single embryo transfer, had a single gestational sac, and a resultant live-born singleton were included. All patients were treated with E2 patches and intramuscular progesterone injections. Main outcome measures were serial E2 and P4, with median values calculated for cycle days 28 (baseline), or 4w0d gestational age (GA), through 60, or 8w4d GA. The baseline cycle day (CD) 28 median value was compared to each daily median cycle day value using the Wilcoxon signed rank test.ResultsA total of 696 patients, 569 using autologous oocytes in programmed FET cycles and 127 using fresh donor oocytes, from 4/2013 to 4/2019 met inclusion criteria. Serum E2 and P4 levels stayed consistent initially and then began to increase daily. Compared to baseline CD 28 E2 (415 pg/mL), the serum E2 was significantly elevated at 542 pg/mL (P < 0.001) beginning on CD 36 (5w1d GA). With respect to baseline CD 28 P4 (28.1 ng/mL), beginning on CD 48 (6w6d GA), the serum P4 was significantly elevated at 31.6 ng/mL (P < 0.001).ConclusionThese results demonstrate that endogenous placental estradiol and progesterone production may occur by CD 36 and CD 48, respectively, earlier than traditionally thought.     

Anti-Müllerian hormone levels as a predictor of the pregnancy rate in women of advanced reproductive age

PurposeTo investigate whether serum anti-müllerian hormone (AMH), follicle stimulating hormone (FSH), or antral follicle count (AFC) are predictive for clinical pregnancy in women who underwent IVF cycles at the age of 35 and olderMethodsA total of 240 consecutive women who underwent IVF cycles at the age of 35 and older were enrolled in this crsoss- sectional study. Pregnant and nonpregnant women were compared.ResultsThe median AMH level of pregnant women was higher than non-pregnant women [3.20 (0.63–9.60) vs 1.15 (0.01–14.90) ng/ml, p < 0.001]. On logistic regression analysis, AMH was an independent predictor of clinical pregnancy rate (CPR) (OR 1.353; 95 % CI 1.141–1.605; P < 0.001). After controlling for the other independent variables (the number of retrieved oocytes, AFC and age), the significant association between AMH and clinical pregnancy rate remained strong (OR 1.677; 95 % CI 1.216–2.311; p = 0.002) on multivariate logistic regression analysis.ConclusionsAMH is an effective measure of quantitative ovarian reserve and it can predict ovarian response to controlled stimulation for advanced age women. The CPR tends to increase as AMH increases.     

Testosterone levels among non-obstructive azoospermic patients 2 years after failed bilateral microdissection testicular sperm extraction: a nested case-cohort study

PurposeTo define the risk of hypogonadism following microdissection testicular sperm extraction in cases of non-obstructive azoospermia. While sperm retrieval by open testicular sperm extraction can be associated with an increased risk of hypogonadism, there is limited data addressing which procedures and which patients harbor the greatest risk.MethodsWe report on a community-acquired, nested, case-cohort of non-obstructive azoospermic patients referred to one clinic after failed bilateral microdissection testicular sperm extraction. Patients were health-matched (1:2) to surgically naïve controls and divided into 2 cohorts based on risk factors for hypogonadism. Among microdissection patients, we compared total testosterone and gonadotropin levels before and > 6 months after surgery. Biochemical hypogonadism was defined as a total serum testosterone level ≤ 300 ng/dL. Hormone levels were compared to risk-matched controls. Comparative statistics were used to assess hormone levels within and between cohorts.ResultsThere were no significant differences in baseline testosterone levels between microdissection patients (n = 26) and risk-matched controls (n = 52). At a mean of 26 months (range 6.2–112.8) post-procedure, mean testosterone levels decreased significantly (73 ng/dL or 16%; CI − 27, − 166; p < 0.01, paired t-test). Among microdissection patients with baseline testosterone > 300 ng/dL, 8/22 (36%) experienced hypogonadism post-procedure. There was a corresponding increase in follicle stimulating hormone (p = 0.05) and a trending increase in luteinizing hormones (p = 0.10).ConclusionA durable decrease in testosterone levels occurs after failed microdissection testicular sperm extraction regardless of baseline risk of hypogonadism. In addition, a significant proportion of eugonadal patients will become hypogonadal after failed testicular microdissection procedures.     

Follicular fluid Aβ40 concentrations may be associated with ongoing pregnancy following in vitro fertilization

Purpose

To determine whether Aβ40 levels in the follicular fluid (FF) of infertile women undergoing IVF demonstrate a relationship with IVF cycle parameters and outcome.

Methods

FF Aβ40 levels were compared between patients achieving ongoing pregnancy and those with unsuccessful cycles. Clinical data such as ongoing pregnancy rate, implantation rate, number of oocytes retrieved, number of 8 cells embryos with ≤5 % fragmants, ratio of 8 cells embryos with ≤5 % fragmants to total embryos per patient and cleavage rate were compared among three percentile groups of Aβ40. CCK-8 method was used to measure the effect of Aβ40 on rat granulosa cells proliferation in vitro. RT-PCR was used to detect the mRNA expression levels of steroidogenesis related genes.

Results

Patients achieving ongoing pregnancy (n = 26; 50.98 %) demonstrated significantly higher FF Aβ40 levels compared to those with unsuccessful cycles (n = 25; 49.02 %; P = 0.024). No significant differences were observed in APP (amyloid precursor protein) and its other proteolysis products including sAPPα, sAPPβand Aβ 42 between the two groups. Statistically significant differences between the three percentile groups of Aβ 40 were observed only in the implantation rates and ongoing pregnancy rates. There were no statistically significant differences between the three percentile groups in the age, No. oocytes retrieved, No. 2 pronucleus, No. embryos transferred, No. 8 cells embryos with ≤5 % fragmants and cleavage rate. Significantly negative correlation exists between APP and AFC (antral follicle count) (R =−0.360, P = 0.005) and oocytes retrieved (R =−0.378, P = 0.004). There were also significantly positive correlations between Aβ40 and Aβ42 (R = 0.407, P = 0.000), between AFC and oocytes retrieved (R = 0.476, P = 0.000). Rat granulosa cells treated with Aβ40 of different concentrations have improved their proliferative ability. Cells treated with 200 pg/ml Aβ40 have the strongest ability of proliferation. 200 pg/ml Aβ40 enhanced the expression of key molecules during steroidogenesis such as IGF-1,IGF-1receptor (IGF-1R),FSH receptor (FSHR),P450 aromatase (P450arom),steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage cytochromes P450(P450scc).

Conclusions

Aβ40 levels in follicle fluid may be associated with ongoing pregnancy and the moderate expression level of Aβ40 is important for oocytes and embryos development.     

Role of Cervical Phosphorylated Insulin-Like Growth Factor-Binding Protein 1 (phIGFBP1) for Prediction of Successful Induction Among Primigravida with Prolonged Pregnancy

Purpose of the StudyTo estimate and to compare the levels of cervical phIGFBP-1 among primigravida with prolonged pregnancy, with and without successful induction of labor (IOL).MethodsA diagnostic study (cross-sectional study design) was conducted in our institution from November 2016 to April 2018 on 84 primigravida at ≥ 41 weeks with uncomplicated singleton pregnancy. The results were analyzed using SPSS software and receiver operating characteristics curves to determine the best cutoff using Youden Index. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive (+ LR) and negative likelihood ratio (− LR) were calculated. P value < 0.05 was considered significant. Logistic regression analysis was used to determine the predictive ability of the three markers for successful IOL.ResultsThe cutoff level of phIGFBP-1, Bishop score (BS) and transvaginal cervical length (TVL) were 7.8 µg/l, 3 and 3.5 cm, respectively. The sensitivity, specificity, PPV, NPV, + LR and − LR of phIGFBP-1 (> 7.8 µg/l) were 0.87, 0.87, 0.89, 0.85, 6.76 and 0.15, respectively. Using logistic regression analysis, phIGFBP-1 was found to be the best predictor of successful IOL (OR 44.200; 95% CI 12.378–157.831, p < 0.001).ConclusionphIGFBP-1 is a strong independent predictor successful IOL as compared to TVL and BS in primigravida with prolonged pregnancy.     

Time intervals between semen production,initiation of analysis,and IUI significantly influence clinical pregnancies and live births

PurposeDoes IDEF mapping help monitor the technical process of IUI and explore the potential improvements which might contribute to increased pregnancy and live birth rates?MethodRetrospective analysis of 1729 homologous IUI cycles of couples attending a fertility clinic in a university hospital setting. Standardized conventional semen parameters were analyzed and the semen samples prepared via discontinuous density gradient centrifugation.ResultsThere was no significant association between sperm concentration, motility and morphology (analysis phase), and pregnancy outcome. Only female and male ages were significantly associated with the pregnancy outcome. There was a significant difference in the odds on clinical pregnancies and live births when analysis was ≤ 21 min initiated, and < 107 min between sample production and IUI, adjusted for male and female age.ConclusionsAdjusting for the couple’s age, we could show that time intervals between semen production and analysis and IUI when kept low significantly influenced clinical pregnancies and live births.     

Does the Addition of Serum PAPP-A and β-hCG Improve the Predictive Value of Uterine Artery Pulsatility Index for Preeclampsia at 11–14 Weeks of Gestation? A Prospective Observational Study

Purpose of StudyTo study the role of uterine artery Doppler pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG) levels, individually and in combination with each other, at 11–14 weeks of gestation for prediction of preeclampsia (PE).MethodsIn a prospective observational study, a total of 100 low-risk gravid females were recruited at 11–14-weeks of gestation. UtA-PI, PAPP-A and fβ-hCG levels were estimated. These women were followed up until delivery for the development of PE and gestational hypertension (GH).ResultsThe best individual marker for screening PE and GH was UtA-PI with ROC AUC (± standard error) = 0.934 ± 0.028, p < 0.0001. UtA-PI at a cutoff value of ≥ 2.8 (95th percentile) had 77.8% sensitivity, 98.9% specificity, 97.8% NPV and 87.5% PPV in detecting PE. PAPP-A (MoM) at a cutoff value of ≤ 0.27 (5th percentile) demonstrated 44.4% sensitivity, 95.6% specificity, 94.5% NPV and 50% PPV. fβ-hCG (MoM) at a cutoff value of ≤ 0.5 (5th percentile) had a specificity of 94.5%. Among the combined markers, UtA-PI along with PAPP-A estimation served best with a sensitivity and specificity of 44% and 100%, respectively. Addition of fβ-hCG to either UtA-PI or PAPP-A levels was not found sensitive for detecting PE but yielded 100% specificity and 96% NPV.ConclusionUtA-PI as a stand-alone test was found most useful for the prediction of PE. Addition of either or both of PAPP-A and fβ-hCG to UtA-PI did not improve the sensitivity of combined test with only a slight improvement in specificity and NPV. Their routine addition to UtA-PI studies is not recommended for prediction of PE at 11–14 weeks of gestation in low- and lower-middle-income countries (LMIC).     

Does reducing gamete co-incubation time improve clinical outcomes: a retrospective study

Purpose

The objective of this retrospective study was to determine whether patients undergoing in vitro fertilization (IVF) benefit from reducing the gamete co-incubation time.

Methods

Patients (n = 570) were enrolled, including 281 patients in the reduced incubation time group (2-h incubation) and 289 patients in the standard IVF group (18-h incubation).

Results

The observed outcomes, including the clinical pregnancy rate (CPR), implantation rate (IR), live birth rate (LBR), and miscarriage rate (MR), were similar between the two groups. When the data were divided into two subgroups based on the maternal age (≤30 and >30 years), the rates of top-quality embryos (30.83 vs. 25.89 %; p = 0.028), CPR (66.67 vs. 42.11 %; p = 0.013), and IR (41.90 vs. 31.25 %, p = 0.019) of the 2-h incubation group were significantly higher in the younger subgroup. However, for older patients, only a lower MR (7.59 vs. 20.83 %; p = 0.019) was achieved. Reducing the time of incubation still improved the CPR (OR = 1.993, 95 % CI 1.141–3.480) and MR (OR = 3.173, 95 % CI 1.013–9.936) in the younger and older subgroups, respectively, after it was adjusted for potential confounders.

Conclusions

Reducing incubation time improves the clinical results of IVF, although the LBR is not statistically different between the 2- and 18-h incubation time groups. And the specific clinical outcomes of reducing incubation time varied between the >30-year-old and the ≤30-year-old.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-015-0618-8) contains supplementary material, which is available to authorized users.     

Predicting Maternal Serum Adiponectin and Leptin Level as Biomarkers of Pre-eclampsia: A Prospective Study

BackgroundThe aim of this study to determine maternal adiponectin and leptin levels as biomarkers of pre-eclampsia and compare adiponectin and leptin ratio. Materials and MethodsThis is a prospective study. The enrolled women were divided into two groups: first, study group (n = 60) comprised of women diagnosed with pre-eclampsia and second, control group (n = 60) comprised of age- and gestation-matched normotensive and nonproteinuric women.Main Outcome MeasuresMaternal serum adiponectin and leptin levels and their ratio were compared in pre-eclamptic (study group) and normotensive (control group) women. ResultsAdiponectin levels were insignificantly higher in study group than control group. Leptin levels in study group were significantly higher than control group (p < 0.001). Adiponectin/leptin ratio was significantly lower in study group than controls (p < 0.0001). Sensitivity, specificity, positive predictive value and negative predictive value of serum leptin and serum adiponectin/leptin ratio as a biomarker of pre-eclampsia were 90%, 88.3%, 88.5%, 89.8% and 68.3%, 90%, 87.2%, 74%, respectively. Serum leptin levels and serum adiponectin/leptin ratio had cut-off point as 23.3 ng/ml and < 0.153, respectively. Accuracy of both serum leptin and adiponectin/leptin ratio was significant (p < 0.0001).ConclusionMaternal leptin-level estimation should be integrated into the investigations for pre-eclampsia, and a cut-off level of > 23.3 ng/ml should be used as a biomarker for diagnosis. Adiponectin–leptin ratio should be considered as a biomarker for PE and should be determined in all cases of pre-eclampsia, and a cut-off of < 0.153 should be used for diagnosis.     

Does IVF cleavage stage embryo quality affect pregnancy complications and neonatal outcomes in singleton gestations after double embryo transfers?

Purposes

Embryo quality is associated with successful implantation and live births. Our retrospective study was carried out to determine whether or not cleavage stage embryo quality affects the miscarriage rate, pregnancy complications and neonatal outcomes of singletons conceived with assisted reproduction technology.

Method

The current study included 11,721 In Vitro Fertilization-Embryo Transfer cycles (IVF-ET) between January 2009 (the date at which electronic medical records were implemented at our center) and March 2013. Only women < 40 years of age undergoing their first fresh embryo transfer cycle using non-donor oocytes were included.

Results

Our study indicated that the transfer of poor-quality embryos resulted in higher miscarriage (19.77 % vs. 13.28 %, p = 0.02) and lower ongoing pregnancy rates (15.33 % vs. 48.06 %, p < 0.001). Logistic regression analysis performed on data derived from 744 cycles culminating in miscarriages versus 4,333 cycles culminating in live births, suggested that embryo quality (p = 0.04) is significantly associated with miscarriage rate after adjusting for other confounding factors. Moreover, there were no differences in the mean birth weight, low birth weight (<2,500 g), very low birth weight (<1,500 g), gestational age, preterm delivery (<37 weeks), very preterm delivery (<32 weeks), congenital malformations, small-for-gestational-age singletons (SGA), and large-for-gestational-age singleton (LGA) rate (p > 0.05). Similarly, pregnancy complications resulting from poor-quality embryos were not different from good-quality embryos (4.04 % vs. 2.57 %, p = 0.33). Finally, logistic regression suggested that embryo quality was not significantly associated with pregnancy complications after adjusting for other confounding factors (p = 0.40).

Conclusions

Our study suggests that transfer of poor-quality embryos did not increase the risk of adverse outcomes; however, the quality of cleavage stage embryos significantly affected the miscarriage rate and ongoing pregnancies.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-014-0351-8) contains supplementary material, which is available to authorized users.