Function of caspase-14 in trophoblast differentiation

Background

It has become an accepted procedure to transfer more than one embryo to the patient to achieve acceptable ongoing pregnancy rates. However, transfers of more than a single embryo increase the probability of establishing a multiple gestation. Single-embryo transfer can minimize twin pregnancies but may also lower live birth rates. This meta-analysis aimed to compare current data on single-embryo versus double-embryo transfer in fresh IVF/ICSI cycles with respect to implantation, ongoing pregnancy and live birth rates.

Methods

Search strategies included on-line surveys of databases from 1995 to 2008. Data management and analysis were conducted using the Stats Direct statistical software. The fixed-effect model was used for odds ratio (OR). Fixed-effect effectiveness was evaluated by the Mantel Haenszel method. Seven trials fulfilled the inclusion criteria.

Results

When pooling results under the fixed-effect model, the implantation rate was not significantly different between double-embryo transfer (34.5%) and single-embryo transfer group (34.7%) (P = 0.96; OR = 0.99, 95% CI 0.78, 1.25). On the other hand, double-embryo transfer produced a statistically significantly higher ongoing clinical pregnancy rate (44.5%) than single-embryo transfer (28.3%) (P < 0.0001; OR:2.06, 95% CI = 1.64,2.60). At the same time, pooling results presented a significantly higher live birth rate when double-embryo transfer (42.5%) (P < 0.001; OR: 1.87, 95% CI = 1.44,2.42) was compared with single-embryo transfer (28.4%).

Conclusion

Meta-analysis with 95% confidence showed that, despite similar implantation rates, fresh double-embryo transfer had a 1.64 to 2.60 times greater ongoing pregnancy rate and 1.44 to 2.42 times greater live birth rate than single-embryo transfer in a population suitable for ART treatment.     

Expectations of assisted conception for infertility.

OBJECTIVE--To provide reliable prognostic information for couples seeking assisted conception. DESIGN--Analysis of four years'' practice (1988-91). SETTING--Private university service linked with NHS reproductive medicine services. PATIENTS--804 couples with various causes of subfertility, median duration five years, median age of women 34 years. INTERVENTIONS--1280 completed cycles: 950 in vitro fertilisation, 144 gamete intrafallopian transfer, and 186 intrauterine insemination and superovulation. MAIN OUTCOME MEASURES--Pregnancy and birth rates per cycle and cumulative pregnancy and take home baby rates per couple. RESULTS--In women under 40 years and men with normal sperm, whatever the cause of infertility, results with in vitro fertilisation improved steadily reaching a pregnancy rate per cycle of 30% (95% confidence interval 26% to 35%) during 1990-1 and birth rate per cycle of 29% (23% to 35%) in 1990. Pregnancy and birth rates for gamete intrafallopian transfer were 36% (28% to 44%) and 26% (17% to 37%) and for intrauterine insemination 18% (12% to 24%) and 16% (10% to 22%). After six cycles cumulative probability of pregnancy was 82% and cumulative take home baby rate 70%. Considering only in vitro fertilisation and gamete intrafallopian transfer after four cycles the pregnancy rate was 78% (66% to 91%). CONCLUSIONS--Conception is less likely in women over 40 and men with sperm dysfunction. For other couples the prognosis for a live birth is at least as good as for fertile couples if they persist with treatment.     

Does routine ultrasound scanning improve outcome in pregnancy? Meta-analysis of various outcome measures.

OBJECTIVE--To evaluate the effectiveness of routine ultrasound scanning in pregnancy by a meta-analysis of various outcome measures. DESIGN--Meta-analysis of randomised controlled trials evaluating the effect of routine ultrasound scanning on perinatal mortality and morbidity. Live birth rate (that is, live births per pregnancy) is included as a measure of pregnancy outcome in addition to the conventional perinatal mortality. SUBJECTS--15,935 pregnancies (7992 in which routine ultrasound scanning was used and 7943 controls with selective scanning) from four randomised controlled trials. MAIN OUTCOME MEASURES--Perinatal mortality, live birth rate, rate of miscarriage, Apgar score < 7 at 1 minute, and number of induced labours. RESULTS--The live birth rate was identical in both screening and control groups (odds ratio = 0.99; 95% confidence interval 0.88 to 1.12) although the perinatal mortality was significantly lower in the group who had routine ultrasonography (0.64, 0.43 to 0.97). Differences in perinatal morbidity between the two groups as measured by the proportion of newborn babies with Apgar score < 7 at 1 minute were not significant (1.05; 0.93 to 1.19). CONCLUSION--Routine ultrasound scanning does not improve the outcome of pregnancy in terms of an increased number of live births or of reduced perinatal morbidity. Routine ultrasound scanning may be effective and useful as a screening for malformation. Its use for this purpose, however, should be made explicit and take into account the risk of false positive diagnosis in addition to ethical issues.     

Elective frozen-thawed embryo transfer (FET) in women at risk for ovarian hyperstimulation syndrome

Elective cryopreservation of cultured embryos has become a treatment option for women at risk for ovarian hyperstimulation syndrome (OHSS). The aim of our study was to investigate the outcome of elective cryopreservation and consecutive frozen-thawed embryo transfer (FET) in a large IVF clinic in Austria. A total of 6104 controlled ovarian hyperstimulation cycles (COH) were performed on 2998 patients including 200 patients (6.7%) who were undergoing elective cryopreservation and FET due to high risk of OHSS. We estimated the cumulative live birth rate using the Kaplan-Meier method and evaluated independent predictors for successful live births with a Cox model. A total of 270 frozen-thawed embryo transfers were performed on 200 patients with up to 4 transfers per patient. The first embryo transfer showed a live birth rate of 42.0%, the second transfer showed a cumulative rate of 58.5%. After a total of 4 FETs from the same COH cycle, a cumulative live birth rate of 61.0% per COH cycle could be achieved. Four cases of OHSS occurred amongst these patients (2.0%), all of them of moderate severity. Multivariate analysis identified maternal age, the use of assisted hatching and the number of embryos transferred at the blastocyst stage as independent predictors for cumulative live birth. Our study clearly suggests that elective FET is safe and shows excellent cumulative live birth rates. This concept can, therefore, be used to avoid the severe adverse events caused by COH and the inefficient use of cultured embryos.     

GnRHa for trigger and luteal phase support in natural cycle frozen embryo transfer – A proof of concept study

We aimed to explore whether ovulation induced by a GnRH analogue (GnRHa), followed by daily GnRHa luteal support provides an efficient platform for natural cycle frozen embryo transfer (NC-FET).In this cohort study, included were normo-ovulatory women who underwent NC-FET cycles, under the age of 40, with an antral follicle count > eight. Ovulation was triggered with triptorelin (0.2 mg Decapeptyl; Ferring), and luteal support was initiated two days later, using a Nafarelin inhaler (Synarel, Pfizer), 200 μg twice daily. Main outcome measures were luteal estradiol and progesterone levels (three to five days following ovulation), implantation rate, ongoing pregnancy rate, early pregnancy loss rate, and live birth rate.Fifty-one patients treated between 2017 and 2018 were included. Mid luteal progesterone levels among study patients, were non-significantly different between patients who achieved pregnancy and those who did not, but differed significantly on day 14 following ovulation (86.0 ± 31.3 vs. 9.8 ± 9.5 nmol/L, respectively, p < 0.001). Twenty-three patients achieved a clinical pregnancy (45.1 %); interestingly, there were no chemical pregnancies. Three pregnancies ended in an early abortion at 6–7 weeks gestation, and 20 pregnancies continued as ongoing pregnancies (39.2 %). One patient had a late abortion at 16 weeks gestation, and 14 had a live birth.In conclusion, in this proof of concept study, inducing ovulation with a bolus of GnRHa in NC-FET, followed by repeated daily GnRHa administration, resulted in satisfactory luteal phase steroid levels and high ongoing pregnancy and live birth rates.     

Blood metal/metalloid concentration of male subjects undergoing IVF/ICSI treatment outcomes: A prospective cohort study

BackgroundPrevious epidemiology studies reported that heavy metal/metalloid exposure is associated with the impairment of semen quality. However, it is still not clear whether the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment outcome will be affected after the heavy metal/metalloid exposure of the male partners.MethodsA prospective cohort study with a 2-year followed-up was conducted in a tertiary IVF center. A total of 111 couples undergoing IVF/ICSI treatment were initially recruited from November 2015 to November 2016. Male blood concentrations of heavy metal/metalloid including Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Mo, Cd, Hg, and Pb were measured by inductively coupled plasma mass spectrometry, and the lab and pregnancy outcome data were followed up. The associations between male blood heavy metal/metalloid concentration and the clinical outcomes were analyzed by Poisson regression analysis.ResultsOur results showed that none of the heavy metal/metalloid of male partners we investigated are significantly associated with the oocyte fertilization and good embryo (P ≥ 0.05); however, antral follicle count (AFC) was a protective factor for the oocyte fertilization (RR: 1.07, 95 % CI: 1.04–1.10). The blood Fe concentration of the male partner was positively associated (P < 0.05) with pregnancy in the first fresh cycle (RR:170.93, 95 % CI: 4.13–7082.04), cumulative pregnancy (RR: 23.61, 95 % CI: 3.25–171.64) and cumulative live birth (RR: 36.42, 95 % CI: 1.21–1092.54). In the first frozen embryo cycles, pregnancy was significantly associated (P < 0.05) with the blood Mn (RR: 0.01, 95 % CI:0.00–0.11) and Se concentration (RR: 0.01, 95 % CI:8.25 E-5–0.47) and female age (RR: 0.86, 95 % CI:0.75–0.99); live birth was significantly associated (P < 0.05) with the blood Mn concentration (RR: 0.00, 95 % CI: 1.14E-7–0.51).ConclusionsOur results suggested that the higher male blood Fe concentration was positively associated with pregnancy in the fresh embryo transfer cycle, cumulative pregnancy, and cumulative live birth, whereas the higher male blood Mn and Se concentration were associated with lower chance of pregnancy and live birth in the frozen embryo transfer cycle. However, the underline mechanism of this finding still needs further investigation.     

Identifying Maternal Constraints on Fetal Growth and Subsequent Perinatal Outcomes Using a Multiple Embryo Implantation Model

IntroductionAlthough the majority of singleton births after in vitro fertilization (IVF) are uncomplicated, studies have suggested that IVF pregnancies may be independently associated with low birth weight (LBW), preterm birth (PTB), and perinatal mortality. These outcomes complicate multiple gestations as expected, but have also been reported in singletons. A multiple embryo implantation model allows for assessment of the early in utero environment, and therefore, assessment of any maternal constraints on developing fetuses. We question whether adverse perinatal outcomes associated with assisted reproductive techniques (ART) occur as a result of maternal physiologic adaptations.ResultsA total of 17,415 cycles were analyzed. The average maternal age was 36.9 (±5.0) years. An overall fertilization rate of 73.4% generated approximately 48,708 good quality cleavage-stage embryos. In most patients (92.8%), an average of 3 embryos were transferred. The clinical pregnancy rate was 39.2% (n = 6,281). The overall occurrence of multiple gestations was 38.2% (n = 2,608) consisting of 2,038 twin, 511 triplet, and 59 quadruplet pregnancies. Of these multiple gestations, 18.6% of twin, 54.2% of triplet and 76.3% of quadruplet gestations spontaneously reduced. Failure of the implanted embryo to progress was not related to maternal age. Singleton newborns resulting from multiple implantation sites had lower birth weights (P<0.01) and shorter gestational ages (P<0.01) than those from a single implanted embryo. The number of embryos transferred did not affect the gestational length of singleton newborns. Although the birth weights of singletons from multiple implantation sites (virtual singletons) were lower than true singletons, the birth weight of virtual singletons were comparable to the birth weights of true twin, triplet, and quadruplet live births. Multiple logistic regression revealed that virtual singletons were an independent risk factor for PTB (odds ratio: 4.55, 95% CI 2.23–9.29) and LBW (odds ratio: 3.61, 95% CI 1.78–7.32), even after controlling for the number of oocytes, stimulation protocol type, sperm source, total gonadotropins administered, age, embryo quality, and day of embryo transfer.ConclusionsOur study highlights that embryonic implantation sites during early gestation set the growth profile of each embryo, dictating later growth patterns. Specifically, spontaneous reduction of an embryo after multiple embryo implantations can confer greater perinatal risk in the form of LBW and PTB to the surviving fetus. Our findings suggest that maternal constraints or physiologic adaptations maybe one of the mechanisms mediating adverse perinatal outcomes when multiple embryo implantation occurs.     

Perinatal mortality and adverse pregnancy outcomes in a low-income rural population of women who smoke

We describe adverse pregnancy outcomes, including congenital anomalies, fetal, neonatal, and infant mortality among a Missouri population of low-income, rural mothers who participated in two randomized smoking cessation trials. In the Baby BEEP (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650 women's pregnancy outcomes known (93.5% retention rate). Following the BB trial, 298 women who had a live infant after November 2004 were recruited again into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population and perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n = 79), 29% were spontaneous abortions of less than 20 weeks' gestation, 23% were premature births, and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1000 births (BB study) compared with 8.6 per 1000 births (state of Missouri) and 8.5 per 1000 births (United States). The postneonatal infant mortality rate was 13.4 per 1000 live births (BBK) compared with 2.1 per 1000 live births (United States). The health disparity in this population of impoverished, rural, pregnant women who smoke, particularly in regard to perinatal and infant deaths, warrants attention.     

The trophectoderm could be better predictable parameter than inner cellular mass (ICM) for live birth rate and gender imbalance

Selection of best blastocyst is crucial in single blastocyst transfer cycles, which is based on blastocyst morphological parameters such as inner cell mass (ICM), trophectoderm (TE) and its inner diameter. We aimed to study relation between morphological parameter and sex ratio after single vitrified-warmed blastocyst transfer (SVBT). Current study based on data of single-center and performed by retrospective analysis of 1563 SVBT (911 patients) with minimal stimulation on 5th and 6th days. TE morphology, female age and blastocyst day are highly correlated with clinical pregnancy rate (CPR) and live birth rate (LBR). Also, A grade ICM significantly correlated with CPR than C grade. Additionally, probability of being male gender is 2.8 times higher in singleton live birth with A grade trophectoderm than C grade. Neither ICM morphology, LBR nor sex ratio were not related to trophoectoderm grade. Higher grade TE, younger the age of patient and selection of the day 5 blastocyst showed higher frequency of CPR and LBR. Therefore, consideration of these parameters is a better method to select the best embryo. On the other hand, the selection for transfer blastocyst based on quality and morphological parameters may inadvertently push the secondary sex ratio (SSR) in favor of female births.     

Predicting live birth, preterm delivery, and low birth weight in infants born from in vitro fertilisation: a prospective study of 144,018 treatment cycles

Background

The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown.

Methods and Findings

We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 (n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth (n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2–23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46–1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99–1.24); p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia.

Conclusions

Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF. Please see later in the article for the Editors'' Summary     

Maternal exposure to exogenous sex hormones in relation to birth weight of offspring

Birth weight was analyzed among singleton live births (N = 665) in Upstate New York in 1974 to women who used oral contraceptives (OC) in comparison to live births to women who used no contraceptives (N = 716), within 11 months prior to last menstrual period (LMP). In addition, birth weight was examined among live births to women who received hormone support therapy (N = 97) and hormone pregnancy tests (N = 75) during pregnancy. There was no evidence for a reduction in mean birth weight, or an increase in frequency of lower weights, among births to OC users, including those who stopped using OC within 2 months of LMP. Generally similar findings held within three maternal age groups (less than 25, 25-29, and 30-39 years). There was no evidence for a reduction in birth weight among offspring of women who received hormone pregnancy tests. Mean birth weight was relatively low among male and female births to women who received hormone therapy for "threatened abortion," but this may reflect the selection of women for such treatment rather than an effect of exogenous hormones on fetal growth.     

In Vitro Maturation in Women with vs. without Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

Objective

To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS.

Study design

A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates.

Results

Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95%CI: 0.99–3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53–3.68) and implantation rates (pooled OR = 1.73, 95%CI: 1.06–2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed.

Conclusion

The present meta-analysis provides preliminary evidence on the effectiveness of IVM as a treatment option when offered in sub-fertile PCOS women, as the latter present at least as high outcome rates as those in non-PCOS.     

Perinatal mortality and adverse pregnancy outcomes in a low‐income rural population of women who smoke

We describe adverse pregnancy outcomes, including congenital anomalies, fetal, neonatal, and infant mortality among a Missouri population of low‐income, rural mothers who participated in two randomized smoking cessation trials. In the Baby BEEP (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650 women's pregnancy outcomes known (93.5% retention rate). Following the BB trial, 298 women who had a live infant after November 2004 were recruited again into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population and perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n = 79), 29% were spontaneous abortions of less than 20 weeks' gestation, 23% were premature births, and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1000 births (BB study) compared with 8.6 per 1000 births (state of Missouri) and 8.5 per 1000 births (United States). The postneonatal infant mortality rate was 13.4 per 1000 live births (BBK) compared with 2.1 per 1000 live births (United States). The health disparity in this population of impoverished, rural, pregnant women who smoke, particularly in regard to perinatal and infant deaths, warrants attention. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.     

High incidence of preterm births and early losses in pregnancy after in vitro fertilisation. Australian in vitro fertilisation collaborative group.

A fertilisation cohort of 244 pregnancies resulting from in vitro fertilisation was reported to a national register by eight units specialising in in vitro fertilisation. Early pregnancy losses were high, with 5% tubal ectopic pregnancies, 18% biochemical pregnancies, and an incidence of spontaneous abortion of 27%. Among pregnancies of at least 20 weeks'' gestation 22% were multiple, with 26 pairs of twins and four sets of triplets. The incidence of preterm births was more than three times higher than in the general population. Low birthweight rates were also higher, owing both to preterm births and to multiple pregnancies. The sex ratio and the incidence of major congenital malformations were similar to those in naturally conceived pregnancies. In this series the high fetal losses at all stages of pregnancy suggested maternal reproductive causes and should not be interpreted as being due to factors peculiar to in vitro fertilisation. Further analysis will be necessary when larger numbers are available.     

Improvement of in vitro fertilisation after treatment with buserelin,an agonist of luteinising hormone releasing hormone

Treatment with buserelin, an agonist of luteinising hormone releasing hormone, and human menopausal gonadotrophin was compared with the conventional treatment of clomiphene citrate and human menopausal gonadotrophin in the outcome of in vitro fertilisation. Seventy seven infertile women had 83 cycles of treatment with buserelin and human menopausal gonadotrophin, and concurrently another 328 infertile women were treated with clomiphene citrate and human menopausal gonadotrophin. Seven (8%) cycles were cancelled owing to inadequate superovulation or ovarian hyperstimulation in the women receiving buserelin and 103 (31%) were cancelled because of poor follicular development in those receiving clomiphene citrate. The mean number of oocytes recovered was significantly higher with buserelin (9·5 (SD 4·5) v 5·5 (2·2)) as was the mean number of embryos obtained (4·3 (2·4) v 2·9 (1·7)). Significantly more women who had an embryo transfer became clinically pregnant after treatment with buserelin (53% (30/57) v 30% (48/159), or 36% v 14% of treatment cycles). Altogether 33% (10) of pregnancies in women treated with buserelin were multiple compared with 23% (11) in those treated conventionally. Of the 17 completed pregnancies in women treated with buserelin, 11 resulted in the birth of live babies (eight singletons, two sets of twins, and one set of triplets) and six failed, five before 12 weeks'' gestation and one at 22 weeks. The 13 continuing pregnancies (32 weeks) were eight singletons, two sets of twins, and three sets of triplets. Of the 48 completed pregnancies in women treated with clomiphene citrate, 35 resulted in the birth of live babies (26 singletons, five sets of twins and four sets of triplets) and 13 failed, eleven before 12 weeks'' gestation and two by 27 weeks.Buserelin increased the chance of pregnancy after in vitro fertilisation compared with conventional treatment, but the risk of multiple pregnancy may be increased.     

A novel isolator-based system promotes viability of human embryos during laboratory processing

In vitro fertilisation (IVF) and related technologies are arguably the most challenging of all cell culture applications. The starting material is a single cell from which one aims to produce an embryo capable of establishing a pregnancy eventually leading to a live birth. Laboratory processing during IVF treatment requires open manipulations of gametes and embryos, which typically involves exposure to ambient conditions. To reduce the risk of cellular stress, we have developed a totally enclosed system of interlinked isolator-based workstations designed to maintain oocytes and embryos in a physiological environment throughout the IVF process. Comparison of clinical and laboratory data before and after the introduction of the new system revealed that significantly more embryos developed to the blastocyst stage in the enclosed isolator-based system compared with conventional open-fronted laminar flow hoods. Moreover, blastocysts produced in the isolator-based system contained significantly more cells and their development was accelerated. Consistent with this, the introduction of the enclosed system was accompanied by a significant increase in the clinical pregnancy rate and in the proportion of embryos implanting following transfer to the uterus. The data indicate that protection from ambient conditions promotes improved development of human embryos. Importantly, we found that it was entirely feasible to conduct all IVF-related procedures in the isolator-based workstations.     

The application of single beta-human chorionic gonadotropin (β-hCG) level measurement in women undergoing single blastocyst transfer

We previously explored the associations between β-hCG on the 14th day post–embryo transfer (ET) and reproductive outcomes and established a series of cutoff values to predict different outcomes. The aim of this study was to explore the parameters associated with β-hCG levels and establish β-hCG cutoff values in women undergoing single blastocyst transfer. The patients were transferred with either fresh or frozen-thawed blastocysts. Serum β-hCG levels were compared among different groups. Cutoff values of β-hCG were established and applied to divide the patients into different groups, among which the β-hCG groups were compared. Develop day negatively affected β-HCG levels in those who were pregnant or gave live birth (P < 0.001, 0.008). Inner cell mass significantly affected β-hCG levels in women who were pregnant or gave live birth (P = 0.013, 0.044). Trophectoderm significantly affected β-hCG levels in women with most reproductive outcomes, except biochemical pregnancy (BP) (P = 0.184). The cutoff values of β-hCG for predicting positive outcomes were 194.1, 503.0, 1048.0, and 2590.5 mIU/L. BP rates and adverse pregnancy outcome rates were significantly lower in the higher β-hCG groups (P < 0.001). Shorter gestational age and lower birth weight and length (P = 0.005, 0.041, 0.003) were observed in the lowest-concentration β-hCG group. The application of a single β-hCG measurement was sufficient to predict reproductive outcome in women undergoing blastocyst transfer, under the full consideration of blastocyst parameters. However, the association between β-hCG and obstetric outcomes remains to be investigated and fully explained.     

Microorganisms within Human Follicular Fluid: Effects on IVF

Our previous study reported microorganisms in human follicular fluid. The objective of this study was to test human follicular fluid for the presence of microorganisms and to correlate these findings with the in vitro fertilization (IVF) outcomes. In this study, 263 paired follicular fluids and vaginal swabs were collected from women undergoing IVF cycles, with various causes for infertility, and were cultured to detect microorganisms. The cause of infertility and the IVF outcomes for each woman were correlated with the microorganisms detected within follicular fluid collected at the time of trans-vaginal oocyte retrieval. Microorganisms isolated from follicular fluids were classified as: (1) ‘colonizers’ if microorganisms were detected within the follicular fluid, but not within the vaginal swab (at the time of oocyte retrieval); or (2) ‘contaminants’ if microorganisms detected in the vagina at the time of oocyte retrieval were also detected within the follicular fluid. The presence of Lactobacillus spp. in ovarian follicular fluids was associated with embryo maturation and transfer. This study revealed microorganisms in follicular fluid itself and that the presence of particular microorganisms has an adverse affect on IVF outcomes as seen by an overall decrease in embryo transfer rates and pregnancy rates in both fertile and infertile women, and live birth rates in women with idiopathic infertility. Follicular fluid microorganisms are a potential cause of adverse pregnancy outcomes in IVF in both infertile women and in fertile women with infertile male partners.     

Role of Baseline Antral Follicle Count and Anti-Mullerian Hormone in Prediction of Cumulative Live Birth in the First In Vitro Fertilisation Cycle: A Retrospective Cohort Analysis

Objective

This retrospective study determined for the first time the role of baseline antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) level in the first in-vitro fertilisation (IVF) cycle in predicting cumulative live birth from one stimulation cycle.

Methods

We studied 1,156 women (median age 35 years) undergoing the first IVF cycle. Baseline AFC and AMH level on the day before ovarian stimulation were analysed. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers after the same stimulation cycle.

Results

Serum AMH was significantly correlated with AFC. Both AMH and AFC showed significant correlation with age and ovarian response in the stimulated cycle and total number of transferrable embryos. Baseline AFC and serum AMH were significantly higher in subjects attaining a live birth than those who did not in the fresh stimulated cycle, as well as those attaining cumulative live birth. There was a significant trend of higher cumulative live birth rate in women with higher AMH or AFC. However, logistic regression revealed that both AMH and AFC were not significant predictors of cumulative live birth after adjusting for age and number of embryos available for transfer. Considering only one single predictor, the areas under the ROC curves for AMH (0.646, 95% CI 0.616–0.675) and age (0.648, 95% CI 0.618–0.677) were slightly higher than that for AFC (0.617, 95% CI 0.587–0.647) in predicting cumulative live birth. However, a model combining AMH (with or without AFC) and age of the women only classified an addition of less than 2% of subjects correctly compared to the model with age alone.

Conclusion

Baseline AFC and serum AMH have only modest predictive performance on the occurrence of cumulative live birth, and may not give additional value on top of the women''s age.     

The Associations between Bridal Pregnancy and Obstetric Outcomes among Live Births in Korea: Population-Based Study

Objective

In East Asia the recently increased number of marriages in response to pregnancy is an important social issue. This study evaluated the association of marriage preceded by pregnancy (bridal pregnancy) with obstetric outcomes among live births in Korea.

Methods

In this population-based study, 1,152,593 first singleton births were evaluated from data registered in the national birth registration database from 2004 to 2008 in Korea. In the study population, the pregnancy outcomes among live births from the bridal pregnancy group (N = 62,590) were compared with the outcomes of the post-marital pregnancy group (N = 564,749), composed of women who gave birth after 10 months but before 24 months of marriage. The variables preterm birth (PTB; <37 weeks gestation) and low birth weight (LBW; <2.5 kg) were used to determine the primary outcome. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated after controlling for socio-demographic factors.

Results

The socio-demographic factors among the bridal pregnancy group were associated with a social disadvantage and particular risk factors. In the subgroup analyses of maternal age, differences in adverse pregnancy outcomes from bridal pregnancy were identified between women in the following age group: (i) ≤19, (ii) 20–39, and (iii) ≥40 years. After the multivariate analysis, the aORs for each age group were 1.47 (95% CI: 1.15–1.89), 1.76 (1.70–1.83), and 1.13 (0.77–1.66), respectively, for PTB and 0.92 (0.70–1.21), 1.60 (1.53–1.66), and 1.11 (0.71–1.74), respectively, for LBW. In the adjusted logistic regression models, bridal pregnancy was associated with PTB (1.76, 1.69–1.82) and LBW (1.53, 1.48–1.59).

Conclusion

Pregnancy outcomes among live births from bridal pregnancies are associated with higher risks for PTB and LBW in Korea.