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Purpose: The objective of this study was to determine whether ammonium accumulates in IVF media during fertility process and whether the brief co-incubation of gametes (bIVF) benefited the outcomes of newborns.Methods: Ammonium levels in IVF media during gamete co-incubation were measured and the effects of bIVF on neonatal outcomes were evaluated retrospectively in this study.Results: A total of 609 live newborns cycles were included in this study. The results showed that ammonium levels in the conventional IVF (cIVF) media was significantly increased than that in bIVF and control media (27.32 ± 5.60 vs 20.71 ± 3.89, P = 0.03; 27.32 ± 5.60 vs 19.46 ± 1.31, P = 0.01, respectively). In the cIVF group, the mean gestational age was significantly lower (37.36 ± 2.29 vs. 37.74 ± 1.94 weeks, P = 0.031) and the incidence of preterm birth (< 37 weeks) was higher than that in the bIVF group (25.80 vs. 17.63%, P = 0.015). Singleton cycles and twin cycles were then analyzed respectively. The gestational age and birth weight of the singleton cycles were similar between the two groups. However, of the twin cycles, the gestational age was significantly decreased and the rate of preterm birth was increased significantly in the cIVF group (35.76 ± 2.31 vs. 36.48 ± 1.73, P = 0.013; 53.33 vs. 31.52%, P = 0.002, respectively).Conclusions: There is an ammonium accumulation in IVF media during co-incubation of gametes. And bIVF reduces the risk of preterm birth (< 37 weeks), especially with regard to preterm birth of the twin cycles, and seems to be a safe alternative method for improving the neonatal outcomes compared with cIVF. [ABSTRACT FROM AUTHOR]

Background Use of organophosphate flame retardants (PFRs) has increased over the past decade following the phase out of some brominated flame retardants, leading to increased human exposure. We recently reported that increasing maternal PFR exposure is associated with poorer pregnancy outcomes among women from a fertility clinic. Because a small epidemiologic study previously reported an inverse association between male PFR exposures and sperm motility, we sought to examine associations of paternal urinary concentrations of PFR metabolites and their partner's pregnancy outcomes. Methods This analysis included 201 couples enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2005–2015) who provided one or two urine samples per IVF cycle. In both the male and female partner, we measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert -butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). The sum of the molar concentrations of the urinary PFR metabolites was calculated. We used multivariable generalized linear mixed models to evaluate the association of urinary concentrations of paternal PFR metabolites with IVF outcomes, accounting for multiple in vitro fertilization (IVF) cycles per couple. Models were adjusted for year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity. Results Detection rates were high for paternal urinary concentrations of BDCIPP (84%), DPHP (87%) and ip-PPP (76%) but low for tb-PPP (12%) and zero for BCIPP (0%). We observed a significant 12% decline in the proportion of fertilized oocytes from the first to second quartile of male urinary ΣPFR and a 47% decline in the number of best quality embryos from the first to third quartile of male urinary BDCIPP in our adjusted models. An 8% decline in fertilization was observed for the highest compared to lowest quartile of urinary BDCIPP concentrations (95% CI: 0.01, 0.12, p-trend = 0.06). Conclusions Using IVF as a model to investigate human reproduction and pregnancy outcomes, we found that paternal urinary concentrations of BDCIPP were associated with reduced fertilization. In contrast to previously reported findings for the female partners, the paternal urinary PFR metabolites were not associated with the proportion of cycles resulting in successful implantation, clinical pregnancy, and live birth. These results indicate that paternal preconception exposure to TDCIPP may adversely impact successful oocyte fertilization, whereas female preconception exposure to ΣPFRs may be more relevant to adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

In vitro fertilization (IVF) is the perfect example of translational research. Changes in IVF and the IVF laboratory have been transmitted to clinical care, showing dramatic improvements in health outcomes, including notable increases in the cumulative pregnancy rate. Current research in the laboratory focusing on culture media, embryo selection criteria, and implementation of genetic testing and manipulation promises to translate to further improvements in our ability to assist human reproduction. The field of IVF and ART remains a large source for clinical and scientific discovery and development, and will require the proper interested and invested personnel, occupational structuring, and funding for continued success. [ABSTRACT FROM AUTHOR]

The main adverse effect of IVF is the high multiple pregnancy rate resulting from the transfer of two or more embryos. The objective was to evaluate pregnancy rates in infertile women with a good prognosis who failed to conceive in a fresh elective single embryo transfer (eSET) and had a second cycle with elective double vitrified-warmed embryo transfer (eDFET) compared with elective single vitrified-warmed embryo transfer (eSFET). A total of 142 intracytoplasmic sperm injection cycles using a conventional protocol were evaluated. Good-prognosis patients underwent eSET in a fresh cycle, and those who failed to conceive underwent a second vitrified-warmed embryo transfer: eDFET ( n = 102) or eSFET ( n = 40). Embryos were transferred and vitrified on day 5 of development. Patients who received eDFET had fewer implantations (30.9%) than eSFET (52.5%; P = 0.004); pregnancy rates were similar (eDFET: 35.3%, eSFET: 42.5%). Patients with the eSFET had one monozygotic twin (5.9%), and 22.2% of eDFET patients had multiple pregnancies. Patients with a good prognosis who failed to conceive in the first fresh eSET did not have an advantage when receiving eDFET in the second cycle, as pregnancy rates were similar; 22.2% of patients in the eDFET group had multiple pregnancies. [ABSTRACT FROM AUTHOR]

This retrospective study assessed the predictive value of endometrial thickness (EMT) on HCG administration day for the clinical outcome of fresh IVF and intracytoplasmic sperm injection (ICSI) cycles. A total of 8690 consecutive women undergoing 10,787 cycles over a 5-year period were included. The 5th, 50th and 95th centiles for EMT were determined as 8, 11 and 15 mm, respectively. Group analysis according to these centiles (Group 1: < 8 mm; Group 2: ≥ 8 and ≤11 mm; Group 3: > 11 and ≤15 mm; Group 4: > 15 mm) demonstrated significant differences ( P < 0.001) in clinical pregnancy rates (23.0%, 37.2%, 46.2% and 53.3%, respectively), live birth rates per clinical pregnancy (63.3%, 72.0%, 78.1% and 80.3%, respectively), spontaneous abortion rates (26.7%, 23.8%, 19.9% and 17.5%, respectively), and ectopic pregnancy rates (10.0%, 4.3%, 2.1% and 2.2%, respectively). Logistic regression analyses showed EMT as one of the independent variables predictive of clinical pregnancy (OR = 1.097; P < 0.001), live birth (OR = 1.078; P < 0.001), spontaneous abortion (OR = 0.948; P < 0.001), and ectopic pregnancy (OR = 0.851; P < 0.001). Future research should aim to understand the underlying mechanisms relating EMT to conception, ectopic implantation and spontaneous abortion. [ABSTRACT FROM AUTHOR]

Cell-derived microparticles (cMPs) are small membrane vesicles that are released from many different cell types in response to cellular activation or apoptosis. Elevated cMP counts have been found in almost all thrombotic diseases and pregnancy wastage, such as recurrent spontaneous abortion and in a number of conditions associated with inflammation, cellular activation and angiogenesis. cMP count was investigated in patients experiencing unexplained recurrent implantation failure (RIF). The study group was composed of 30 women diagnosed with RIF (RIF group). The first control group (IVF group) ( n = 30) comprised patients undergoing a first successful IVF cycle. The second control group (FER group) included 30 healthy women who had at least one child born at term and no history of infertility or obstetric complications. cMP count was significantly higher in the RIF group compared with the IVF and FER groups ( P < 0.05 and P < 0.01, respectively) (RIF group: 15.8 ± 6.2 nM phosphatidylserine equivalent [PS eq]; IVF group: 10.9 ± 5.3 nM PS eq; FER group: 9.6 ± 4.0 nM PS eq). No statistical difference was found in cMP count between the IVF and FER groups. Increased cMP count is, therefore, associated with RIF after IVF and embryo transfer. [ABSTRACT FROM AUTHOR]

MTHFR is an important enzyme in the metabolism of folic acid and is crucial for reproductive function. Variation in the sequence of MTHFR has been implicated in subfertility, but definitive data are lacking. In the present study, a detailed analysis of two common MTHFR polymorphisms (c.677C>T and c.1298A>C) was performed. Additionally, for the first time, the frequencies of different MTHFR alleles were assessed in preimplantation embryos. Several striking discoveries were made. Firstly, results demonstrated that maternal MTHFR c.1298A>C genotype strongly influences the likelihood of a pregnancy occurring, with the 1298C allele being significantly overrepresented amongst women who have undergone several unsuccessful assisted reproductive treatments. Secondly, parental MTHFR genotypes were shown to affect the production of aneuploid embryos, indicating that MTHFR is one of the few known human genes with the capacity to modulate rates of chromosome abnormality. Thirdly, an unusual deviation from Hardy-Weinberg equilibrium was noted for the c.677C>T polymorphism in subfertile patients, especially those who had experienced recurrent failure of embryo implantation or miscarriage, potentially explained by a rare case of heterozygote disadvantage. Finally, a dramatic impact of the MTHFR 677T allele on the capacity of chromosomally normal embryos to implant is described. Not only do these findings raise a series of interesting biological questions, but they also argue that testing of MTHFR could be of great clinical value, identifying patients at high risk of implantation failure and revealing the most viable embryos during in vitro fertilisation (IVF) cycles. [ABSTRACT FROM AUTHOR]

In vitro activation (IVA) represents a new frontier in the treatment of women with primary ovarian insufficiency as well as patients with cancer desiring fertility preservation. Here, we review the biological basis of IVA and the recent translation of IVA to humans by targeting Hippo and Akt-signaling pathways. We then provide a new integrated viewpoint on IVA, highlighting basic science research on the aspects of follicular development and ovarian tissue transplantation which may potentially optimize future translational research on IVA. Specific topics discussed include cryopreservation techniques, additional IVA pathway targets, the roles of actin polymerization, paracrine and endocrine factors, and the role of mechanical signaling and associated tissue rigidity in controlling ovarian follicular activation. Further research and improved understanding is needed to optimize success of IVA. [ABSTRACT FROM AUTHOR]

There have been no studies analyzing the effect of large aggregates of tubular smooth endoplasmic reticulum (aSERT) after conventional in vitro fertilization (cIVF). The aim of this study was to investigate whether aSERT can be identified after cIVF and the association between the embryological outcomes of oocytes in cycles with aSERT. This is a retrospective study examining embryological data from cIVF cycles showing the presence of aSERT in oocytes 5–6 h after cIVF. To evaluate embryo quality, cIVF cycles with at least one aSERT-metaphase II (MII) oocyte observed (cycles with aSERT) were compared to cycles with normal-MII oocytes (control cycles). Among the 4098 MII oocytes observed in 579 cycles, aSERT was detected in 100 MII oocytes in 51 cycles (8.8%). The fertilization rate, the rate of embryo development on day 3 and day 5–6 did not significantly differ between cycles with aSERT and control group. However, aSERT-MII oocytes had lower rates for both blastocysts and good quality blastocysts (p < 0.05). aSERT can be detected in the cytoplasm by removing the cumulus cell 5 h after cIVF. However, aSERT-MII oocytes do not affect other normal-MII oocytes in cycles with aSERT. [ABSTRACT FROM AUTHOR]

In the 17th issue of News from the Biological Stain Commission (BSC) under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the 20th meeting of ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on October 15 − 17, 2014 in Toronto, Canada, and from the 29th meeting of CEN/TC 140 In vitro diagnostic medical devices held on February 3, 2015 in Berlin, Germany. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate that oocyte cryopreservation is a feasible reproductive option for patients with cancer of childbearing age who require gonadotoxic therapies.Methods: This study is a university-based retrospective review of reproductive-aged cancer patient treatment cycles that included ovarian stimulation, transvaginal oocyte retrieval, oocyte cryopreservation, and, in some cases, subsequent oocyte thaw, in vitro fertilization, and embryo transfer. Outcome measures included ovarian stimulation response, number of oocytes retrieved, cryopreserved, and thawed, and pregnancy data.Results: From 2005 to 2014, 176 reproductive-aged patients with cancer (median age 31 years, interquartile range 24-36) completed 182 oocyte cryopreservation cycles. Median time between consult request and oocyte retrieval was 12 days (interquartile range 10-14). Median peak stimulation estradiol was 1,446 pg/mL (interquartile range 730-2,687); 15 (interquartile range 9-23) oocytes were retrieved and 10 (interquartile range 5-18) metaphase II oocytes were cryopreserved per cycle. Ten patients (11 cycles) have returned to attempt pregnancy with their cryopreserved oocytes. Among thawed oocytes, the cryopreservation survival rate was 86% (confidence interval [CI] 78-94%). Nine of 11 thaw cycles resulted in embryos suitable for transfer. The embryo implantation rate was 27% (CI 8-46%) and the live birth rate was 44% (CI 12-77%) per embryo transfer. Chance for live birth with embryos created from cryopreserved oocytes was similar between the patients with cancer in this study and noncancer patients who underwent the same treatment at our center (44% [CI 12-77%] compared with 33% [CI 22-44%] per embryo transfer).Conclusion: Oocyte cryopreservation is now a feasible fertility preservation option for reproductive-aged patients with cancer who require gonadotoxic therapies. [ABSTRACT FROM AUTHOR]

This study aimed to explore the parameters associated with poor ovarian response (POR) to develop an early warning score model (EWSM) for detecting POR in Chinese women undergoing in vitro fertilization, in order to improve the outcomes. Between 2005 and 2011, we recruited 736 patients with POR after IVF and 736 individuals with normal ovarian response after IVF as controls. Clinical parameters were determined to evaluate the ovarian reserve. We then compared the clinical parameters between the POR and control groups, and performed a multivariate analysis to determine the independent factors associated with ovarian response. Receiver-operator characteristic (ROC) was used to analyze the predicted values of individual and combined risk factors. The predicted values were further tested in another cohort of 957 patients. Age, basal follicle-stimulating hormone (bFSH), antral follicle count (AFC), and FSH/luteinizing hormone (LH) ratio were identified as independent factors associated with ovarian response. The EWSM was established using a combination of these parameters. The sensitivity and specificity of the EWSM were 74.6% and 93.6%, respectively. In conclusion, combination of individual risk factors could predict POR with high specificity. The EWSM may help in the evaluation of IVF treatment at an early stage. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to evaluate the use of hysteroscopic Essure device placement for the treatment of hydrosalpinx (HS)-related infertility in patients with laparoscopic contraindications and compared their pregnancy outcomes following IVF–ICSI treatment with those patients having had laparoscopic tubal occlusion (LTO). Patients: From 2008 to 2014 a total of 50 patients were diagnosed with unilateral or bilateral hydrosalpinges: 29 patients had laparoscopic contraindications and were treated hysteroscopically and 21 patients were treated with laparoscopical salpingectomy. Results: Of the 29 patients who underwent treatment with Essure®, 21 began a cycle of in vitro fertilization (IVF), and 13 finished in embryo transfer that resulted in seven clinical pregnancies. Furthermore, in the group of women treated with salpingectomy, 17 started an IVF cycle that resulted in 12 clinical pregnancies. The clinical pregnancy rate per patient with an IVF cycle started was 33.3% and 70.6%, the live-birth rate per patient was 14.3% and 52.9%, the miscarriage rate was 57.1% and 18.2%, and the implantation rate was 16.3% and 34.1% for hysteroscopy and laparoscopy, respectively. Conclusion: Essure® placement is an alternative method for occlusion of hydrosalpinges before IVF. Monitoring the live-birth rate confirms that this option may be considered when laparoscopy is impossible or contraindicated. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether intracytoplasmic sperm injection (ICSI) can improve the clinical outcomes of the male patients with teratozoospermia in the ultra-short term GnRH-a protocol. Methods: Based on different normal sperm morphology rate (NSMR), the patients were divided into three groups as follows: NSMR = 0% group, 1% ≤NSMR <4% group and NSMR ≥4% group. Each group was compared with two fertilization type ofin-vitrofertilization (IVF) and ICSI separately. Main outcomes compared were normal fertilization, high-quality embryo, transferrable embryo, implantation, pregnancy and abortion rate. Results: We observed that the total clinical pregnancy rate in single cleavage-stage embryo transfer (SET) group was significantly lower compared with double cleavage-stage embryo transfer (DET) group (23.87% versus 40.08%;p < 0.001). There was no significant difference in the aspects of female age, endometrial thickness, infertility duration and the number of retrieved oocytes among three groups (p > 0.05). The normal fertilization, high-quality embryo, transferrable embryo, implantation, pregnancy and abortion rate of IVF and ICSI showed no significant difference among three groups (p > 0.05). Conclusion: ICSI cannot improve clinical outcomes of the patients with teratozoospermia in the ultra-short term GnRH-a protocol. [ABSTRACT FROM PUBLISHER]

This open label randomized study aims to define the best protocol to be used with growth hormone in poor responders, with comparison performed to delineate which protocol offers the best cycle outcomes. Two-hundred eighty-seven poor responders were included. The patients were randomly allocated into four groups receiving growth hormone (GH) as an adjuvant therapy added to either long or short agonist protocol, miniflare or antagonist protocols. The short/GH gave significantly lower mean number of oocytes when compared with the long/GH, antagonist/GH and miniflare/GH (4 ± 1.69 versus 5.06 ± 1.83, 4.95 + / = 1.90 and4.98 ± 2.51, respectivelyp = 0.005). Considering the number of fertilized oocytes, the long/GH showed significantly higher levels than short/GH and antagonist/GH (3.73 ± 1.47 versus 3.02 ± 1.52 and 2.89 ± 1.14, respectively). The main drawback is that it required significantly higher HMG dose and longer duration of stimulation. The long/GH was superior when compared with the three protocols regarding the number of oocytes retrieved and fertilized. But, when considering the clinical pregnancy rates, there was a difference in favor of the long/GH but not reaching a statistically significant value (ClinicalTrials.gov Identifier: NCT01897324). [ABSTRACT FROM PUBLISHER]

Background: Lifestyle factors including cigarette smoking, alcohol consumption and nutritional habits impact on health, wellness, and the risk of chronic diseases. In the areas of in-vitro fertilization (IVF) and pregnancy, lifestyle factors influence oocyte production, fertilization rates, pregnancy and pregnancy loss, while chronic, low-grade oxidative stress may underlie poor outcomes for some IVF cases. Methods: Here, we review the current literature and present some original, previously unpublished data, obtained from couples attending the PIVET Medical Centre in Western Australia. Results: During the study, 80 % of females and 70 % of male partners completed a 1-week diary documenting their smoking, alcohol and fruit and vegetable intake. The subsequent clinical outcomes of their IVF treatment such as quantity of oocytes collected, fertilization rates, pregnancy and pregnancy loss were submitted to multiple regression analysis, in order to investigate the relationship between patients, treatment and the recorded lifestyle factors. Of significance, it was found that male smoking caused an increased risk of pregnancy loss (p = 0.029), while female smoking caused an adverse effect on ovarian reserve. Both alcohol consumption (ß = 0.074, p < 0.001) and fruit and vegetable consumption (ß = 0.034, p < 0.001) had positive effects on fertilization. Conclusion: Based on our results and the current literature, there is an important impact of lifestyle factors on IVF clinical outcomes. Currently, there are conflicting results regarding other lifestyle factors such as nutritional habits and alcohol consumption, but it is apparent that chronic oxidative stress induced by lifestyle factors and poor nutritional habits associate with a lower rate of IVF success. [ABSTRACT FROM AUTHOR]

Introduction: Tubal pregnancy is often treated by surgery: salpingotomy or salpingectomy. Concern has been raised regarding the risk of compromising the vascular and nervous supply to the ovary, following salpingectomy. The aim of this study was to investigate whether the ovarian response to controlled ovarian stimulation for in vitro fertilization (IVF) is reduced after salpingectomy in comparison with salpingotomy, among women undergoing IVF subsequent to surgical treatment of tubal pregnancy.Material and Methods: This retrospective cohort study included 153 women who had undergone IVF after surgery for ectopic tubal pregnancy. Women treated by either salpingectomy or salpingotomy constituted the two groups. Potential confounders (age, body mass index, smoking, stimulation dosage of gonadotrophin and reason for IVF) were included in multivariable regression analyses. The primary outcome was number of retrieved oocytes. The secondary outcomes were clinical pregnancy and live birth rates.Results: A total of 118 women had undergone unilateral salpingectomy and 35 women had undergone unilateral salpingotomy. The mean number of oocytes at aspiration in the subsequent IVF cycle was 11.8 (salpingectomy group) and 11.7 (salpingotomy group). A linear regression analysis showed no effect of treatment type on aspirated oocytes [β = -0.11, 95% confidence interval -2.27, 2.04 (p = 0.92)]. Adjustment for potential confounders did not alter the result.Conclusion: Among women undergoing IVF after surgery for tubal pregnancy, the ovarian response was not influenced by the surgical method. Our results do not support the theory that salpingectomy, compared with salpingotomy, impairs ovarian reserve measured as number of oocytes retrieved during subsequent IVF treatment. [ABSTRACT FROM AUTHOR]

We observed the effects of changes in progesterone (P) during late follicular phases on the treatment outcome ofin vitrofertilization-embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI) in patients with different ovarian responses. The data of 8,575 cycles of patients receiving gonadotropin-releasing hormone (GnRH) agonist using the long protocol were retrospectively analyzed. According to the number of oocytes retrieved, the cycles were divided into poor ovarian response group (oocyte retrieval <5), intermediate ovarian response group (5≤ oocyte retrieval ≤15), and high ovarian response group (oocyte retrieval ≥16). We found that in the poor ovarian response group, the clinical pregnancy rate was not significantly associated with both the level of P or the day of human chorionic gonadotrophin (hCG) and the duration of pre-hCG P elevation (p = 0.66 andp = 0.1874). In intermediate and high ovarian response groups, the clinical pregnancy rate was inversely related to both the level of P on the day of hCG administration and the duration of pre-hCG P elevation (allp < 0.0001). The cut-off values of serum P level on the day of hCG administration were 1 ng/ml and 1.75 ng/ml in intermediate and high ovarian response groups, respectively. The cut-off values of pre-hCG P elevation duration were obtained on day 1 in the intermediate ovarian response group, and days 1 or 3 in the high ovarian response group. After correcting for other confounding factors, multivariate logistic regression analysis indicated that P level on the day of hCG administration was not associated with clinical pregnancy rates, but pre-hCG P elevation duration was negatively associated with clinical pregnancy rate in the intermediate and high ovarian response groups. P level is associated with clinical pregnancy rate only in the patients with intermediate or high ovarian response. The longer the duration of pre-hCG P 1 ng/ml, the lower the clinical pregnancy rate. [ABSTRACT FROM PUBLISHER]

During the human in vitro fertilization procedure in the assisted reproductive technology, intracytoplasmic sperm injection is routinely used to inject a spermatozoon or a less mature elongating spermatid into the oocyte. In some infertile men, round spermatids (haploid male germ cells that have completed meiosis) are the most mature cells visible during testicular biopsy. The microsurgical injection of a round spermatid into an oocyte as a substitute is commonly referred to as round spermatid injection (ROSI). Currently, human ROSI is considered a very inefficient procedure and of no clinical value. Herein, we report the birth and development of 14 children born to 12 women following ROSI of 734 oocytes previously activated by an electric current. The round spermatids came from men who had been diagnosed as not having spermatozoa or elongated spermatids by andrologists at other hospitals after a first Micro-TESE. A key to our success was our ability to identify round spermatids accurately before oocyte injection. As of today, all children born after ROSI in our clinic are without any unusual physical, mental, or epigenetic problems. Thus, for men whose germ cells are unable to develop beyond the round spermatid stage, ROSI can, as a last resort, enable them to have their own genetic offspring. [ABSTRACT FROM AUTHOR]

Background: Poor ovarian response phenomenon has been observed in some of the in vitro fertilization-embryo transfer patients. Some investigations found that follicle stimulating hormone receptor (FSHR) gene plays a role in the process, but no direct evidence shows the correlation between genotypes of FSHR and ovarian response. Objective: Exploring the molecular mechanism behind the mutation of FSHR promoter association with ovarian granulosa cells and poor ovarian response. Materials and Methods: This cross sectional study was performed using 158 women undergoing the controlled short program ovarian stimulation for IVF treatment. The 263 bp DNA fragments before the follicle stimulating hormone (FSH) receptor 5' initiation site were sequenced in the patients under IVF cycle, 70 of which had poor ovarian response and 88 showed normal ovarian responses. Results: With a mutation rate of 40%, 63 in 158 cases showed a 29th site G→A point mutation; among the mutated cases, the mutation rate of the poor ovarian responders was significantly higher than the normal group (60% versus 23.9%; Χ2=21.450, p<0.001). Besides, the variability was also obvious in antral follicle count, and ovum pick-ups. The estradiol peak values and the number of mature eggs between the two groups had significant difference. However, there was no obvious variability (t=0.457, p=0.324) in the basic FSH values between the two groups (normal group, 7.2±2.3 U/L; mutation group, 7.1±2.0 U/L). Conclusion: The activity of FSHR promoter is significantly affected by the 29th site G→A mutation that will weaken promoter activity and result in poor response to FSH. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether prolongation of the time interval between HCG administration and oocyte retrieval, from 36 h to 38 h, affects oocyte retrieval rate in women undergoing ovarian stimulation with gonadotrophins and GnRH antagonists for IVF. One hundred and fifty-six normo-ovulatory women were randomized to have oocyte retrieval performed 36 h ( n = 78) or 38 h ( n = 78) following HCG administration. Oocyte retrieval rate was defined as number of cumulus–oocyte–complex (COC) retrieved/follicle ≥11 mm present on day of HCG administration. No significant differences were observed between the groups regarding baseline characteristics. Moreover, no significant difference was observed between the groups regarding oocyte retrieval rate (difference: + 1.2%, 95% CI for difference between medians: −4.5 to +12.1). The median (95% CI for the median) was not significantly different between the groups regarding number of cumulus-oocyte-complexes (COCs) retrieved: 5.5 (5.0–7.0) versus 6.0 (5.0–6.2), respectively, and fertilization rates: 57.7% (50.0–66.7) versus 50.0% (44.8–65.5), respectively. Live birth rates were similar between the groups (20.5% versus 16.7%, RD: + 3.8%, 95% CI: −8.5 to +16.1, respectively). Prolongation of time interval between HCG administration and oocyte retrieval from 36 h to 38 h does not affect oocyte retrieval rate. [ABSTRACT FROM AUTHOR]

This study evaluated the prevalence of asthma and asthma medication use in 213 4-year-old singletons followed from birth onwards, including three groups of children born following: (i) controlled ovarian hyperstimulation IVF/intracytoplasmic sperm injection (ICSI); (ii) modified natural cycle IVF/ICSI; and (iii) natural conception in subfertile couples. The rate of asthma medication was higher in the ovarian hyperstimulation-IVF/ICSI than in the subfertile group (adjusted odds ratios [aOR]: 1.96 [1.00–3.84]). Time to pregnancy, a proxy for the severity of subfertility, was not associated with asthma and asthma medication. In conclusion, controlled ovarian hyperstimulation-IVF/ICSI is associated with the use of asthma medication in 4-year-old offspring of subfertile couples. [ABSTRACT FROM AUTHOR]

Although IVF has been performed routinely for many years to help couples with fertility problems and in relation to modern breeding of farm animals, pregnancy rates after transfer to a recipient have not improved during the last decade. Early prediction of the viability of in-vitro developed embryos before the transfer to a recipient still remains challenging. Presently, the predominant non-invasive technique for selecting viable embryos is based on morphology, where parameters such as rates of cleavage and blastocyst formation as well as developmental kinetics are evaluated mostly subjectively. The simple morphological approach is, however, inadequate for the prediction of embryo quality, and several studies have focused on developing new non-invasive methods using molecular approaches based particularly on proteomics, metabolomics and most recently small non-coding RNA, including microRNA. This review outlines the potential of several non-invasive in-vitro methods based on analysis of spent embryo culture medium. [ABSTRACT FROM AUTHOR]

While the need for progesterone-based luteal phase support is well documented, the required treatment duration is not well established, and a practitioners' survey showed a wide range of empiric stopping points. It is suggested that an early stop can be based on assessing endogenous luteal activity on the day of pregnancy test. To examine this approach, data were retrospectively collected on 99 patients with positive pregnancy test and high serum concentrations of oestradiol and progesterone (≥1000 pmol/l and ≥110 nmol/l, respectively), whose luteal support was stopped, and compared with those of 85 patients who did not meet the above criteria, and so luteal support was continued until gestational week 9. Both groups were comparable in terms of live birth and miscarriage rates. We conclude that in the face of strong endogenous luteal activity, exogenous support can be stopped on pregnancy test day, without affecting pregnancy outcome. Further research is needed to substantiate this finding. [ABSTRACT FROM AUTHOR]

The article discusses research concerning the significant of in vitro diagnostic (IVF) diagnostic test on biological samples from a living body, such as urine, blood and tissue to determine or confirm the existence of disease in an individual. Topics include IVF's accessible diagnosis without invasive surgeries, prevent from biological safety problems in patients and quick valuable information concerning the healthcare conditions of patients.

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The effects of oocyte aging on meiotic spindle dynamics have been well recognised, but the mechanisms underlying the effects are not well understood. In this paper we review the role of centrosomes and the microtubule cytoskeleton in meiotic spindle formation and maintenance, and the impact of oocyte aging on spindle integrity resulting in centrosome and microtubule dysfunctions that are associated with aneuploidy. Loss of spindle integrity includes dispersion of proteins from the centrosome core structure and loss of attachment of microtubules to centrosomes and kinetochores, which will result in abnormal chromosome separation. The inability of centrosomal proteins to accurately associate with the centrosome structure may be the result of destabilisation of the core structure itself or of microtubule destabilisation at the centrosome-facing microtubule areas that are acetylated in fresh oocytes but may not be acetylated in aging oocytes. Microtubule destabilisation prevents accurate motor-driven transport of centrosomal proteins along microtubules to form and maintain a functional centrosome. Other factors to form and maintain the MII spindle include signal transductions that affect microtubule dynamics and stability. Understanding the mechanisms underlying centrosome and microtubule dysfunctions during oocyte aging will allow diagnosis and analysis of oocyte quality and abnormalities as important aspects for targeted treatment of aging oocytes to extend or restore viability and developmental capacity. New therapeutic approaches will allow improvements in reproductive success rates in IVF clinics, as well as improvements in reproductive success rates in farm animals. This review is focused on: (1) centrosome and microtubule dynamics in fresh and aging oocytes; (2) regulation of centrosome and/or microtubule dynamics and function; and (3) possible treatments to extend the oocyte's reproductive capacity and viability span. Chromosomal abnormalities, increased spontaneous abortion and reduced fertility are associated with maternal aging which has resulted in increased demands for assisted reproductive technologies (ARTs) to increase the chances for the birth of a healthy baby. The aim of this study was to review the mechanisms leading to chromosomal abnormalities in aging oocytes with focus on centrosome and microtubule dynamics in the meiotic MII spindle that are affected by maternal aging but can be treated with specific chemicals to delay or reverse the aging effects. Such treatments may find applications for ART procedures in in vitro fertilisation (IVF) clinics to increase the success rates for the birth of healthy babies. [ABSTRACT FROM AUTHOR]

Background: The effect of progesterone elevation (PE) on the day of human chorionic gonadotropin (hCG) administration on the pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles is a matter of ongoing debate. The replacement of cleavage-stage embryos with blastocyst-stage embryos for transfer was proposed to avoid the possible impairment of PE in fresh cycles. This study aimed to assess the association between PE on the day of human chorionic gonadotropin (hCG) administration and clinical pregnancy rates (CPRs) in IVF/ICSI cycles with embryos transferred at different developmental stages (cleavage and blastocyst). Moreover, a secondary aim was to determine the thresholds at which PE has a detrimental effect on CPRs. Methods: This single-center retrospective cohort study included more than 10,000 patients undergoing day 3 cleavage-stage embryo transfer (ET) and 1146 patients undergoing day 5 blastocyst-stage embryo transfer (ET) using gonadotropin and GnRH agonist for controlled ovarian stimulation. Results: Serum PE was inversely associated with CPRs in both cleavage- and blastocyst-stage ET cycles. In the day 3 ET cycles, CPRs (progesterone levels < 0.5 ng/ml, 49.2 %) significantly declined when the progesterone concentration reached 1.0 ng/ml (45.5 %) and decreased further when the progesterone concentration increased to 1.5 ng/ml (36.2 %). In the day 5 blastocyst-stage ET cycles, patients with serum progesterone levels >1.75 ng/ml had significantly lower CPRs (31.3 % VS. 41.4 %, p < 0.001) compared to patients with serum progesterone levels <1.75 ng/ml. The negative association of PE with CPRs was noted in both ET groups, even after adjusting for confounders. Furthermore, the developmental stage of the transferred embryos was not linked to the effect of PE on CPRs because the interaction between the developmental stage of the transferred embryos and PE was not significant. Conclusions: PE on the day of hCG administration is associated with decreased CPRs in GnRH agonist IVF/ intracytoplasmic sperm injection (ICSI) cycles regardless of the developmental stage of the transferred embryos (cleavage versus blastocyst stage). [ABSTRACT FROM AUTHOR]

Increased utilization of in vitro fertilization (IVF) to treat infertility has resulted in a growing twin birthrate. Despite early childhood risks, twins have fewer psychosocial problems in middle childhood than singleton children. This study proposes that parents' conformity expectations for children have differential effects on parent-child relationships for twin and singleton children, which indirectly explains twins' more optimum psychosocial adjustment. Parental conformity expectations, parent-child relationship satisfaction, and children's emotional, behavioral, and attention problems were assessed in a sample of 288 6- to 12-year-old IVF-conceived twins and singletons. Overall, parents of twins had higher expectations for child conformity to parent rules than singleton parents. Path models demonstrate that twin status and parental expectations for child conformity interact to influence parent-child relationships, and this interaction indirectly accounted for differences in twins' and singletons' psychosocial adjustment. Findings suggest parenting constructs have differential influences on the association between twin status and parent-child relationships. Parenting research, predominantly conducted with singletons, should be reexamined before applying existing research to twin children and their families. [ABSTRACT FROM AUTHOR]

Culture systems are available for human granulosa cells (GCs) that perpetuate luteinization. The present study examines the plating density effects and long-term serum-free culture on the in vitro dynamics differentiation of luteinizing human GCs. Cells were cultured in serum-free α-minimum essential medium (α-MEM) or serum-based tissue culture medium (TCM). The time course of GCs morphology and secretion of estradiol (E2), progesterone (P4), and relaxin were analyzed after 48, 96, and 144 hours of culture. Other functional markers as follicle-stimulating hormone/luteinizing hormone receptors and steroidogenic enzymes were investigated at the end of culture. The morphology of an α-MEM cell rather than a TCM cell resembles more closely that seen in vivo. Compared to TCM cultures, α-MEM cells secreted 93.7% and 87.2% more E2 and approximately 7% and 17% of the amount of P4 when cultured at densities of 2 × 104 or 4 × 104 cells/well, respectively. Relaxin secretion was significantly reduced in α-MEM cultures. α-MEM cells were estrogenic and expressed the CYP19 gene. Levels of CYP17 increased about 8-fold in α-MEM cells above the levels found in TCM cells. Our results reveal new insights into human GCs differentiation in vitro and demonstrate the critical importance of the culture system and cell-plating density on the establishment of estrogenic or progestogenic GC phenotypes. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether ovarian stimulation for IVF increases the risk of gynaecological cancer, including ovarian, endometrial, cervical and breast cancers, as an independent risk factor. A systematic review and meta-analysis was conducted. Clinical trials that examined the association between ovarian stimulation for IVF and gynaecologic cancers were included. The outcomes of interest were incidence rate of gynaecologic cancers. Twelve cohort studies with 178,396 women exposed to IVF were included; 10 studies were used to analyse ovarian (167,640 women) and breast (151,702 women) cancers, and six studies were identified in the analysis of endometrial (116,672 women) and cervical cancer (114,799 women). Among these studies, 175 ovarian, 48 endometrial, 502 cervical and 866 cases of breast cancer were reported. The meta-analysis found no significant association between ovarian stimulation for IVF and increased ovarian, endometrial, cervical and breast cancer risk (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.85 to 1.32; OR 0.97, 95% CI 0.58 to 1.63; OR 0.43, 95% CI 0.30 to 0.60; OR 0.69, 95% CI 0.63 to 0.76, respectively). Ovarian stimulation for IVF, therefore, does not increase the gynaecologic cancer risk, whether hormone-dependent endometrial and breast cancer or non-hormone-dependent ovarian and cervical cancer. [ABSTRACT FROM AUTHOR]

In this systematic review and meta-analysis, the effect of ovarian endometrioma on ovarian responsiveness to stimulation and on assisted reproduction outcomes was evaluated. Nine published studies (1039 cases) were included. The number of oocytes retrieved (mean difference [MD] −1.50; 95% CI, −2.84 to −0.15, P = 0.03), metaphase II (MII) oocytes retrieved (MD −3.61; 95% CI −4.44 to −2.78, P < 0.00001) and total embryos formed (MD −0.66; 95% CI −1.13 to −0.18, P = 0.007) were significantly lower in women with ovarian endometrioma than the control group. Gonadotrophin dose, duration of stimulation, number of good-quality embryos, implantation rate, clinical pregnancy rate and live birth rate were similar. Comparisons between ovaries with endometriomas and healthy ovaries of the same individuals were also made. Number of oocytes retrieved, MII oocytes retrieved and total embryos formed were not statistically significantly different between the affected ovaries and contralateral normal ovaries. Observational studies showed that ovarian endometrioma was associated with fewer oocytes retrieved, fewer MII oocytes retrieved and fewer total formed embryos. Clinical pregnancy rate and live birth rates were not affected. Intra-patient comparisons in women with unilateral endometrioma suggested the number of oocytes retrieved, MII oocytes retrieved and total embryos formed were similar. [ABSTRACT FROM AUTHOR]

Background: Vitamin D in complex with its receptor by regulating gene expression, endometrium immune response and stimulation of endometrium decidualization can be involved in implantation. So, it seems that the amount of vitamin D in follicular fluids (FF) may have an association with ART success. Objective: First, we intended to investigate the possible association between levels of follicular fluids 25-OH vitamin D with assisted reproductive outcomes. Second, we examined relationship between 25-OH vitamin D levels with number and quality of oocytes. Materials and Methods: In a prospective study, 80 infertile female candidates for IVF/ICSI were enrolled. Blood samples (on the day of human chorionic gonadotropin administration) and follicular fluids were taken, and then levels of serum estradiol and follicular fluids 25-OH vitamin D were measured. Also clinical characteristics of patients (duration of infertility, causes of infertility, menstrual status), number and quality of oocytes, number of fertilized oocytes, estradiol levels, and clinical pregnancy were evaluated. Results: Concentration of FF 25-OH vitamin D in pregnant women was significantly higher than non-pregnant women (p=0.007) but there were no significant differences in age, body mass index (BMI), duration of infertility, menstrual status, number of oocytes, oocytes quality, number of fertilized oocytes, and serum estradiol levels between the two groups. Statistically positive correlation was found between 25-OH vitamin D levels with patient age and implantation rate (r=0.264, p=0.018 and r=0.301, p=0.007 respectively). Conclusion: The obtained results suggest that vitamin D without affecting the number and quality of oocytes can independently improve implantation rate and IVF outcome. [ABSTRACT FROM AUTHOR]

Reprogramming in mammalian cell development is currently a scientific hotspot of cell biology, translational medicine, and so on, due to its extensive prospect of application in somatic cell nuclear transplantation (SCNT), induced pluriponent stem cell (iPS) and regenerative medicine. Epigenetic modification is major reprogramming, including DNA methylation, histone post-translational modifications, genomic imprinting, non-coding RNAs,and so on, which regulates genome expression via different mechanisms. For instance, the development and maturation of oocyte is closely associated with the de novo methylation of genome, demethylation of meiosis genes, post-translational histone modifications, etc. Besides, the oocyte provides an optimal reprogramming environment for the demethylation and other reprogramming processes of male pronucleus genome via their reciprocal interactions. The reprogramming in oocyte development and further fertilization, as well as its significance in embryonic development, was reviewed, and the effect of oocyte's environment on the reprogramming of penetrated male pronucleus during natural fertilization was also discussed. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the pregnancy outcomes of those patients with balanced reciprocal translocations after conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), and to provide valuable reference for genetic counseling and assisted reproductive technology (ART) treatment. Methods: Forty- one patients with balanced reciprocal translocation (the study group) and 751 couples with normal karyotypes (the control group) were included. Clinical pregnancy outcomes were compared between the two groups. Results: In the study group, 24 patients were treated with IVF, while other patients treated with ICSI. Additionally, 28 patients were diagnosed as primary infertility, and 11 patients had a history of adverse pregnancy or childbearing. There were not significant differences in the maternal age, number of retrieved oocytes, number of M II oocytes, number of transferred embryo, clinical pregnancy rate, late abortion rate, ectopic pregnancy rate, fetal malformation rate, stillbirth rate, live birth rate, live birth rate per ovum pick-up (OPU) cycle between the two groups (P>0.05). However, there was significant differences in the embryo implantation rate and early miscarriage rate (P<0.05). Nineteen patients in the study group delivered a total of 22 babies in 27 pregnancy cycles. Conclusions: Those balanced reciprocal translocation carrier could achieve an ideal pregnancy outcome when treated with conventional IVF/ICSI and prenatal diagnosis which is an economical and effective treatment for those patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the toxic effect of mono-(2-ethylhexyl) phthalate (MEHP) on steroidogenesis in human granulosa cells(GCs). Methods: Follicular fluid were collected from six patients undergoing in vitro fertilization. GCs were extracted and cultured in vitro for 72 hours, and then treated with MEHP (25, 300, 500 µmol/L). After treatment for 48 hours, the expression levels of CYP11A1, PPAR- γ, CYP19A1 and 3β-HSD mRNAs were determined by real-time PCR. Results: The expression of CYP19A1 mRNA in GCs was significantly down-regulated by MEHP treatment of 300 µmol/L and 500 µmol/L (P<0.05), and the expression of CYP11A1 was significantly down-regulated by MEHP treatment of 500 µmol/L(P<0.05). Also, the expression of 3β-HSD mRNA was decreased by 500 µmol/L MEHP treatment (P<0.05), while PPAR-γ expression was increased by 300 µmol/L and 500 µmol/L MEHP treatment (P<0.05). Conclusions' MEHP at higher doses affects steroidogenesis in GCs by down-regulating the expressions of steroid biosynthesis enzymes CYP11A1, CYP11A1 and 3β-HSD, and by up-regulating the expression of PPAR-γ. [ABSTRACT FROM AUTHOR]

Obesity is associated with decreased pregnancy rates due, in part, to compromised oocyte quality. The aim of the present cross-sectional study of 84 women undergoing oocyte aspiration was to: (1) compare insulin, lipids and glucose in follicular fluid with serum; (2) determine whether increased body mass index (BMI) and waist circumference, hyperinsulinaemia, dyslipidaemia or metabolic syndrome altered follicular fluid metabolites; and (3) determine relative lipid content in oocytes to reveal any influence of these parameters on oocyte quality and IVF outcomes. Insulin, glucose, triglyceride and free fatty acids were lower in follicular fluid than blood and not strictly correlated between compartments. Insulin, glucose and triglyceride positively correlated with increasing BMI and waist circumference in blood and follicular fluid. Insulin increased in follicular fluid in association with metabolic syndrome. Free fatty acid composition analysis showed saturated fatty acids, particularly palmitic and stearic acid, to be more prevalent in follicular fluid than blood. There were no associations between follicular fluid metabolites or oocyte lipid content and clinical outcomes; however, oocyte immaturity correlated with follicular fluid glucose and fatty acid levels, as well as metabolic syndrome. The present study confirms that the human ovarian follicular environment surrounding the oocyte exhibits a unique metabolite profile compared with blood, with distinct localisation of lipids within follicular fluid and oocytes. Obesity is associated with compromised oocyte quality. This study examined lipids within human follicular fluid and oocytes to determine whether they are altered by obesity or associated with oocyte quality. The results show that the ovarian follicular environment, which surrounds and nourishes the oocyte, exhibits a distinct metabolite profile compared to blood; but do not reveal associations between these parameters on and IVF outcomes [ABSTRACT FROM AUTHOR]

Background:Women with ulcerative colitis (UC), who require ileal pouch anal anastomosis (IPAA), have up to a threefold increased incidence of infertility. To better counsel patients who require colectomy, we examined the success rates of in vitro fertilization (IVF) among women who have undergone IPAA.Methods:This was a retrospective cohort study conducted at the Brigham and Women's Hospital and Beth Israel Deaconess Medical Center. Female patients with UC were identified via ICD-9 codes and cross-referenced with those presenting for IVF from 1998 through 2011. UC patients with IPAA were compared with the following two unexposed groups that underwent IVF: (1) patients with UC, who had not undergone IPAA, and (2) patients without inflammatory bowel disease (IBD). The primary outcome was the cumulative live birth rate. Secondary outcomes included number of oocytes retrieved, proportion of patients who underwent embryo transfer, pregnancy rate, and live birth rate at first cycle.Results:There were 22 patients with UC and IPAA, 49 patients with UC and without IPAA, and 470 patients without IBD. The cumulative live birth rate after six cycles in the UC and IPAA groups was 64% (95% confidence interval (CI): 44-83%). This rate did not differ from the cumulative live birth rate in the UC without IPAA group (71%, 95% CI: 59-83%; P=0.63) or the group without IBD (53%, 95% CI: 48-57%; P=0.57).Conclusions:This study demonstrates that in our cohort, women who undergo IPAA achieve live births following IVF at comparable rates to women with UC without IPAA and to women without IBD. [ABSTRACT FROM AUTHOR]

Background: Ectopic pregnancy (EP) is the leading cause of maternal morbidity and mortality during the first trimester and the incidence increases dramatically with in vitro fertilisation and embryo transfer (IVF-ET). The co-existence of an EP with a viable intrauterine pregnancy (IUP) is known as heterotopic pregnancy (HP) affecting about 1% of patients during assisted conception. EP/HP can cause significant morbidity and occasional mortality and represent diagnostic and therapeutic challenges, particularly during fertility treatment. Many risk factors related to IVF-ET techniques and the cause of infertility have been documented. The combination of transvaginal ultrasound (TVS) and serum human chorionic gonadotrophin (hCG) is the most reliable diagnostic tool, with early diagnosis of EP/HP permitting conservative management. This review describes the risk factors, diagnostic modalities and treatment approaches of EP/HP during IVF-ET and also their impact on subsequent fertility treatment. Methods: The scientific literature was searched for studies investigating EP/HP during IVF-ET. Publications in English and within the past 6 years were mostly selected. Results: A history of tubal infertility, pelvic inflammatory disease and specific aspects of embryo transfer technique are the most significant risk factors for later EP. Early measurement of serum hCG and performance of TVS by an expert operator as early as gestational week 5 can identify cases of possible EP. These women should be closely monitored with repeated ultrasound and hCG measurement until a diagnosis is reached. Treatment must be customised to the clinical condition and future fertility requirements of the patient. In cases of HP, the viable IUP can be preserved in the majority of cases but requires early detection of HP. No apparent negative impact of the different treatment approaches for EP/HP on subsequent IVF-ET, except for risk of recurrence. Conclusions: EP/HP are tragic events in a couple's reproductive life, and the earlier the diagnosis the better the prognosis. Due to the increase incidence following IVF-ET, there is a compelling need to develop a diagnostic biomarker/algorithm that can predict pregnancy outcome with high sensitivity and specificity before IVF-ET to prevent and/or properly manage those who are at higher risk of EP/HP. [ABSTRACT FROM AUTHOR]

Background: Intrauterine injection of human chorionic gonadotropin (hCG) at embryo transfer (ET) has been shown to improve the outcome of assisted reproductive techniques. The aim of this study was to confirm previous findings. Methods: In this randomized controlled trial, 483 infertile women who were candidates for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) for the first time were randomly assigned to receive an intrauterine injection of 500 IU hCG or placebo (tissue culture media) before ET. The main outcome measures were implantation and clinical pregnancy rates. Results: Both the hCG-treated group (n = 240) and control group (n = 243) were similar at baseline in terms of demographic and obstetrical characteristics.There were significant differences between the two groups regarding the implantation rate (23.6 vs. 12.2%, p < 0.001), pregnancy rate (54.6 vs. 35.8%, p < 0.001), clinical pregnancy rate (50 vs. 32.1%, p < 0.001), ongoing pregnancy rate (15.3 vs. 9.2%, p < 0.001) and live delivery rate (14.3 vs. 8.4%, p < 0.001). The rate of fertilization and abortion rates were not statistically different. Conclusion: Intrauterine injection of hCG before ET improves implantation and pregnancy rates and may be considered an adjuvant in IVF/ICSI. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The effectiveness of combined co-treatment with aspirin, doxycycline, prednisolone, with or without oestradiol patches, was investigated on live birth (LBR) rates after fresh and frozen embryo transfers (FET) in IVF and intracytoplasmic sperm injection cycles. Cases ( n = 485) and controls ( n = 485) were extensively matched in a one-to-one ratio on nine physical and clinical parameters: maternal age, body mass index, smoking status, stimulation cycle number, cumulative dose of FSH, stimulation protocol, insemination method, day of embryo transfer and number of embryos transferred. No significant differences were found in fresh cycles between cases and controls for the pregnancy outcomes analysed, but fewer surplus embryos were available for freezing in the combined adjuvant group. In FET cycles, LBR was lower in the treatment group (OR: 0.49, 95% CI 0.25 to 0.95). The lower LBR in FET cycles seemed to be clustered in patients receiving combined adjuvant treatment without luteal oestradiol (OR 0.37, 95% CI 0.17 to 0.80). No difference was found in LBR between cases and controls when stratified according to the number of previous cycles (<3 or ≥3). There is no benefit of this combined adjuvant strategy in fresh IVF cycles, and possible harm when used in frozen cycles. [ABSTRACT FROM AUTHOR]

Artificial oocyte activation has been proposed as a suitable means to overcome the problem of failed or impaired fertilization after intracytoplasmic sperm injection (ICSI). In a multicentre setting artificial oocyte activation was applied to 101 patients who were diagnosed with fertilization abnormalities (e.g. less than 50% fertilized oocytes) in a previous conventional ICSI cycle. Female gametes were activated for 15 min immediately after ICSI using a ready-to-use Ca 2+ -ionophore solution (A23187). Fertilization, pregnancy and live birth rates were compared with the preceding cycle without activation. The fertilization rate of 48% in the study cycles was significantly higher compared with the 25% in the control cycles ( P < 0.001). Further splitting of the historical control group into failed (0%), low (1–30%) and moderate fertilization rate (31–50%) showed that all groups significantly benefitted ( P < 0.001) in the ionophore cycle. Fewer patients had their embryo transfer cancelled compared with their previous treatments (1/101 versus 15/101). In total, 99% of the patients had an improved outcome with A23187 application resulting in a 28% live birth rate (35 babies). These data suggest that artificial oocyte activation using a ready-to-use compound is an efficient method. [ABSTRACT FROM AUTHOR]

The development of an objective and accurate test that could help select embryos with the highest chance of achieving pregnancy in IVF procedures is an important goal of reproductive medicine. For this purpose, cumulus cell gene expression is being studied to find biomarkers of pregnancy. Several recent studies have proposed potential biomarkers of pregnancy expressed in cumulus cells; however, these have mostly not been validated on an independent set of samples. The aim of this study was to analyse the expression of EFNB2, RGS2 and VCAN genes proposed as biomarkers of pregnancy in cumulus cells by quantitative polymerase chain reaction. Gene expression was evaluated in 43 individual cumulus cell samples, derived from a highly homogenous group of 43 women. The same protocol for ovarian stimulation was used for all women, and elective single embryo transfer was performed. Expression levels of RGS2 and VCAN did not differ between cumulus cells of implanted and non-implanted embryos. EFNB2 showed borderline higher expression in cumulus cells of non-implanted embryos, which is contradictory to previous studies. Altogether, the results of previous studies in which EFNB2, RGS2 and VCAN were proposed as biomarkers of pregnancy could not be replicated in our set of cumulus cell samples. [ABSTRACT FROM AUTHOR]

Scheduling gonadotrophin-releasing hormone antagonist (GnRH-ant) cycles for IVF intracytoplasmic sperm injection in patients is a challenge because of unpredictable ovum retrieval procedures on weekends, when less manpower is available. Recently, the use of GnRH-ant pre-treatment to delay an IVF and intracytoplasmic sperm injection (ICSI) cycle showed no negative effect on clinical pregnancy rates. An age-matched, case-control study was conducted to evaluate the effectiveness of such pre-treatment for scheduling purposes. Patients ( n = 140) undergoing their first ovarian stimulation for IVF–ICSI were included. Patients starting their stimulation on Tuesdays or Wednesdays were most likely to have their ovum retrieval procedure on Saturdays. Seventy patients received a 3-day course of GnRH-ant before starting stimulation, and were compared with 70 age-matched controls not receiving pre-treatment. The main outcomes were the proportion of ovum retrieval procedures occurring on Saturdays, clinical pregnancy rate and live birth rates. A five-fold reduction in the number of ovum retrievals occurred on Saturdays compared with controls (7.1% versus 34.3%; OR 0.15; 95% CI 0.05 to 0.42; P < 0.001), with no significant differences in clinical pregnancy rate (40.9% versus 37.5%) and live birth rate (27.3% versus 31.3%). GnRH-ant pre-treatment is an effective tool for scheduling of GnRH-ant cycles. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: Does IVF affect the biochemical pregnancy rate? SUMMARY ANSWER: The likelihood of an early pregnancy loss maybe lower and is certainly not higher in IVF cycles when compared with published rates of biochemical pregnancy in fertile women ≤42 years old. WHAT IS KNOWN ALREADY: The use of gonadotrophins to stimulate multi-folliculogenesis alters endometrial expression of genes and proteins, compared with unstimulated cycles. Exogenous estrogen and progesterone taken for endometrial preparation in frozen embryo transfer cycles, also cause changes in endometrial gene and protein expression .These endometrial alterations may compromise the ability of embryos to develop once implanted, possibly increasing the biochemical pregnancy rate. STUDY DESIGN, SIZE, DURATION: This is a retrospective study, involving 1636 fresh and 188 frozen, single embryo transfer (SET) IVF cycles performed between August2008 and December2012. The biochemical pregnancy rate of the 1824 combined IVF and frozen cycles were compared with fertile controls, derived from the three prospective studies in the medical literature that evaluate this rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subjects ≤42-years old, who underwent a SET, as part of afresh or thawed IVF cycle were considered for inclusion. Each subject is represented only once. The biochemical pregnancy rates were compared with those of historical standard, fertile populations with spontaneous conceptions. MAIN RESULTS AND THE ROLE OF CHANCE: The pregnancy rates per transfer for fresh and frozen IVF cycles were similar at 39 and 40%, respectively. There was also no significant difference in the likelihood of pregnancy outcomes (clinical, biochemical and ectopic pregnancy) between fresh IVF and frozen cycles (85.4 versus 85.6%, 13.8 versus 14.8%, 0.5 versus 0%, P = 0.82). However, pregnancy rates decreased in older patients when compared with younger ones P, 0.0001. The biochemical pregnancy rate for fresh and frozen IVF cycles combined was 13.8% of all pregnancies. IVF and frozen cycles were combined as the IVF group treated with hormones for further comparison with the fertile control group. The biochemical pregnancy rate (14%) in the IVF group was lower than the rate based on the total fertile group (18%), P = 0.01 and differed significantly from the rate in two out of the three studies used to establish the normative rate. The age ranges of the IVF and fertile controls were 21 -42 years. The mean age in the IVF population was 34.8 years, as compared with 29 years, 29, 4 years and 30.6 years (Zinaman) in the three published studies (mean: 29.4 years). LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study and it was impossible to recruit an in-house biochemical pregnancy control population. WIDER IMPLICATIONS OF THE FINDINGS: Lower early pregnancy wastage after IVF may be due to the opportunity to select the embryo for transfer. This finding should be confirmed in further studies but supports the idea that embryo selection is an important step. STUDY FUNDING/COMPETING INTEREST(S): None. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS),a common clinical endocrine disorder, is the main cause of anovulatory infertility in women of childbearing age. Due to the particular endocrine disorders in PCOS patients, it is hard to predict ovarian responses to drugs during controlled ovarian stimulation (COS). So, poor ovarian responses and ovarian hyperstimulation syndrome (OHSS) are incredibly common. The common protocols used in IVF for PCOS patients include long protocol, antagonist protocol, mild stimulation protocol, revised super-long protocol, super-long protocol and in vitro maturation (IVM). Presently, long protocol is most frequently used in most of reproductive centers. At the same time, antagonist protocol and mild stimulation protocol, as new protocols, are gradually favored by many clinicians. Super-long protocol and the revised super-long protocol, as the improved traditional protocols, have also obtained good clinic results. IVM,as a technical innovation, can simplify treatment and reduce the risk of OHSS. During IVF for patients with PCOS,it is the key point for clinicians to choose the optimal and economical treatment, to get high -quality eggs and embryos, and to avoid complications such as OHSS. [ABSTRACT FROM AUTHOR]

As the advances in treatment of neoplasia, the protection of female fertility is attaching more and more attention. The application of embryo cryopreservation in IVF center brings definite benefits to some patients. However, there are limitations in embryo cryopreservation. The ovarian tissue cryopreservation is a new research area, in which the cryopreservation technology is the first problem. Two ways of ovarian tissue cryopreservation are slow freezing and vitrification. Compared with the freezing ways using in the piece of ovarian tissue, the directional freezing is a preponderant method for the whole ovary. The directional freezing can keep the whole ovary at the same cooling rate, which is thought to reduce the injury during the whole cooling process. Different freezing protocols have different effects on functional recovery of the frozen-thawed ovarian tissue. It is important to explore the suitable and standard protocol to optimize the efficiency of cryopreservation. Those optimal protocols of ovarian tissue cryopreservation were discussed in this review, so as to provide some references for clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical outcomes by BMI in infertile patients with assisted reproductive treatment, so as to guide the reasonable clinical treatment. Methods: We searched CBM,Wanfang, CNKI, VIP,PubMed and FMJS. Those randomized controlled trails(RCTs) or clinical controlled trails(CCT) were identified, which focused on the comparison of clinical outcomes in infertile patients with IVF-ET%ICSI treatment by BMI (between BMI>25 kg/m² and BMI≤25 kg/m²). The duration of search was from January 2000 to June 2014. The extracted data were analyzed by RevMan 5.0. Results: Six literatures with 2 297 cycles were selected for Meta analysis. Meta analysis showed that the pregnancy rate [0R=0.72,95%C/ (0.58,0.90), %=0.004],birth rate [0R=0.65, 95%CI (0.47,0.91), P=0.01] in the high BMI group (BMI>25 kg/m²) were significantly lower than those in the low BMI group(BMI≤25 kg/m²);and the abortion rate [0R=1.70,95%CI(1.23, 2.35),P=0.001] was significantly higher than that in the low BMI group (BMI≤25 kg/m²). There were not significant differences in the incidence of ectopic pregnancy [0R=1.51,95%CI (0.71,3.22), P=0.28] and the cycle cancellation rate [OR=1.06,95%CI (0.70,1.62), P=0.77] between two groups. Conclusions: It is necessary to ask those infertile women with high BMI to control body weight, and to lower BMI before their ART treatment, so as to improve their clinical outcomes of ART treatment. [ABSTRACT FROM AUTHOR]

Objective: To study the association between the volume size of single follicular and iVF-ET/ iCSi outcomes, in which the ultrasound was used to observe the single follicular developmental state in natural cycles and minimal stimulation cycles. Methods: Clinical data of 1 480 women undergoing iVF-ET/iCSi in our center between April 2007 and May 2012 were retrospectively analyzed. They were divided into 5 groups according to the follicular volume size:group A,≥ 5.5 mL;group B,4.5-5.0 mL,group C,3.5-4.0 mL,group D, 2.5-3.0 mL,group E, 1.0-2.0 mL. The clinical outcomes were compared. Results: 1Follicular volume was significantly decreased with the mean diameter of single follicle on the day of hCG administration in 5 groups, in both non-stimulation protocol and minimal stimulation protocol (P<0.001). 2In natural cycles, the pregnancy rate and live birth rate were relatively low in group A (11.8%), while those rates in other four groups were 20.0%-25.0% and 15.8%-20.0%, but there were not significant differences in groups (P >0.05). in group A,the available transplantation embryo rate was high while the non-fertilization rate was low; the zero oocyte retrieval rate(32.6%) was higher than those in group C and group D(P<0.01); the available transplantation embryo cycle was merely 39.53%(17/43). In group B,the 2PN rate was high while the abnormal fertilization and the not-done fertilization rate were low; the non-fertilization rate was relative high while the available transplantation embryo cycle was merely 48.19% (40/83). The results of other C groups were better than group A generally. 3In minimal stimulation cycles, the pregnancy rates were high in group B and C (24.1% and 21.6%), but there were not significant differences when compared with three other groups (16.7%-17.8%, P >0.05). There were significant differences in the rates of fertilization, abnormal fertilization, good embryo and available transplantation embryo among five groups (P<0.05). The abnormal fertilization rate in group B was relatively high (15.4%) and the available transplantation embryo rate and the good embryo rate were highest (97.0% and 87.8%, respectively). The good embryo rate and the available transplantation embryo rate in group E were lowest (58.1% and 75.8%, respectively,P<0.01). The fertilization rate in group C was lowest and the abnormal fertilization rate was also lowest (3.0%,P<0.01). Conclusions:IVF-ET/ICSI outcomes may be better when the volume of single follicle was 2.5-5.0 mL(15.1-19.6 mm of oocyte diameter). However, it is necessary to have more well-designed and multicenter studies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate factors associated with second-trimester pregnancy loss in patients with normal uterine anatomy who conceived through in vitro fertilization. METHODS: Women aged 21-44 years with ongoing in vitro fertilization pregnancy (at least one fetus with fetal heart tones at 12 weeks of gestation) atan academic hospital from 2001 to 2012 were eligible for inclusion in this retrospective cohort. Comprehensive uterine evaluation permitted inclusion of only women with anatomically normal uterine cavities. Maternal and clinical characteristics associated with spontaneous second-trimester pregnancy loss (between 12 1/7 and 23 6/7 weeks of gestation) were assessed. Multivariable logistic regression generated adjusted odds ratios (ORs), 95% confidence intervals (CIs), and Wald two-sided P values. RESULTS: Among ongoing second-trimester pregnancies, 60 (2.1%) ended in spontaneous pregnancy loss and 2,841 (97.9%) ended in live birth. Multiple gestations (twins or more) conferred greater odds of pregnancy loss (adjusted OR 1.93, CI 1.15-3.24, P=.01) and were more prevalent among losses (48.3%) than live births (34.1%). Uterine leio-myomas were present in 16.7% of losses and 4.7% of live births and were associated with a nearly fourfold increased odds of second-trimester pregnancy loss (adjusted OR 3.82, CI 1.85-7.89, P<.001). Women with obese body mass index ([BMI] 30 or higher) at cycle start experienced twofold greater odds of pregnancy loss compared with normal-weight women (adjusted OR 2.38, CI 1.05-5.65, P=.04). There were eight obese women (32%) among losses and 209 obese women (16.5%) among live births. In vitro fertilization treatment parameters were not associated with odds of second-trimester loss nor were maternal age, ethnicity, or history of recurrent pregnancy loss. CONCLUSION: Odds of second-trimester spontaneous pregnancy loss among in vitro fertilization conceived pregnancies were greater with multiple gestations, leio-myomas, and obese maternal BMI. [ABSTRACT FROM AUTHOR]