المؤلفون: Sunkara, Sesh Kamal¹ sesh.sunkara1@nhs.net, LaMarca, Antonio², Polyzos, Nikolaos P.³, Seed, Paul T.⁴, Khalaf, Yakoub⁵

المصدر: Human Reproduction. Oct2016, Vol. 31 Issue 10, p2261-2267. 7p. 1 Diagram, 2 Charts, 2 Graphs.

مصطلحات موضوعية: *CHILDBIRTH, *PREMATURE labor, *PREGNANCY complications, *FERTILIZATION in vitro, *HEALTH outcome assessment, *LOW birth weight, *BIRTH rate, *GESTATIONAL age, *PREMATURE infants, *EVALUATION of medical care, *INDUCED ovulation, *PREGNANCY, PERINATAL care

مستخلص: Study Question: Does ovarian stimulation affect perinatal outcomes of preterm birth (PTB) and low birth weight (LBW) following IVF treatment.Summary Answer: Despite no significant differences in the risks of PTB and LBW between stimulated and unstimulated IVF in the present study, the study cannot exclude the effect of ovarian stimulation on the perinatal outcomes following IVF.What Is Already Known: Pregnancies resulting from assisted reproductive treatments (ART) are associated with a higher risk of pregnancy complications compared to spontaneously conceived pregnancies attributed to the underlying infertility and the in vitro fertilization techniques. It is of interest to determine the effect size of ovarian stimulation use in achieving a live birth and whether ovarian stimulation that is routinely used in IVF, affects perinatal outcomes of birth weight and gestational age at delivery compared to unstimulated IVF.Study Design, Size, Duration: Anonymous data were obtained from the Human Fertilisation and Embryology Authority (HFEA), the statutory regulator of ART in the UK. The HFEA has collected data prospectively on all ART performed in the UK since 1991. Data from 1991 to 2011 comprising a total of 591 003 fresh IVF ± ICSI cycles involving 584 835 stimulated IVF cycles and 6168 unstimulated IVF cycles were analyzed.Participants/materials, Setting, Methods: Data on all women undergoing either stimulated or unstimulated fresh IVF ± ICSI cycles during the period from 1991 to 2011 were analyzed to compare live birth rates, singleton live birth rates, perinatal outcomes of PTB, early PTB (<32 weeks), LBW and very LBW (<1500 grams) among singleton live births. Adjusted logistic regression was performed for each perinatal outcome for confounding factors: female age, period of treatment, cause of infertility, number of previous IVF cycles and previous live birth.Main Results and the Role Of Chance: Analysis of the large nationwide data demonstrated 3.5 times (95% confidence interval (CI): 3.1-3.9) as many unstimulated IVF cycles being required to achieve one live birth compared to stimulated IVF and 2.9 times (95% CI: 2.6-3.2) as many unstimulated IVF cycles being required to achieve one singleton live birth compared to stimulated IVF. There was no significant difference in the unadjusted odds for PTB (odds ratio (OR) 1.27, 95% CI: 0.80-2.00) and LBW (OR 1.48, 95% CI: 0.90-2.42) between stimulated and unstimulated IVF cycles. There was no significant difference in the risk of the adverse perinatal outcomes after adjusting for potential confounders; PTB (adjusted odds ratio (aOR) 1.43, 95% CI: 0.91-2.26) and LBW (aOR 1.58, 95% CI: 0.96-2.58).Limitations, Reasons For Caution: Although the analysis was adjusted for a number of important confounders, the dataset had no information on smoking, body mass index (BMI) and the medical history of women during pregnancy to allow adjustment. Anonymized nature of the dataset did not make it permissible to analyse one cycle per woman. Given the smaller number of perinatal events with unstimulated IVF, a larger study is needed to investigate further.Wider Implications Of the Findings: Analysis of this large dataset demonstrates that ovarian stimulation has a vital role in maximizing efficacy of IVF. Although there were no significant differences for PTB and LBW following stimulated compared to unstimulated IVF, the CIs were wide enough to include possible clinically important effects.Study Funding/competing Interests: No funding was obtained. There are no competing interests to declare. [ABSTRACT FROM AUTHOR]

المؤلفون: Sunkara, Sesh Kamal¹ sksunkara@hotmail.com, La Marca, Antonio², Seed, Paul T.³, Khalaf, Yacoub³

المصدر: Human Reproduction. Jun2015, Vol. 30 Issue 6, p1473-1480. 8p. 1 Diagram, 5 Charts, 2 Graphs.

مصطلحات موضوعية: *RISK factors in premature labor, *PREGNANCY complications, *BIRTH weight, *PREMATURE infants, *HUMAN in vitro fertilization, *CHILDBIRTH, *OVUM, *HEALTH outcome assessment

مستخلص: STUDY QUESTION: Is there a relation between the number of oocytes retrieved following ovarian stimulation and obstetric outcomes of preterm birth (PTB) and low birthweight (LBW) following IVF treatment? SUMMARY ANSWER: There is an increased risk of PTB (<37 weeks gestation) and LBW (<2500 g) following IVF in women with a high number (>20) of oocytes retrieved. WHAT IS KNOWN ALREADY: Pregnancies resulting from assisted reproductive treatments (ART) are associated with a higher risk of pregnancy complications compared with spontaneously conceived pregnancies. Whether ovarian ageing in women with poor ovarian response is associated with an increased risk of adverse obstetric outcomes is debated. It is also unclear if an excessive response and high egg numbers following ovarian stimulation have an association with adverse obstetric outcomes. STUDY DESIGN, SIZE, DURATION: Observational study using anonymized data on all IVF cycles performed in the UK from August 1991 to June 2008. Data from 402 185 IVF cycles and 65 868 singleton live birth outcomes were analysed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on all women undergoing a stimulated fresh IVF cycle with at least one oocyte retrieved between 1991 and June 2008 were analysed for birth outcomes. Logistic regression analysis of the association between ovarian response (quantified as number of oocytes retrieved) and outcomes of PTB and LBW was performed. MAIN RESULTS AND THE ROLE Of CHANCE: There was a significantly higher risk of adverse obstetric outcomes of PTB and LBW among women with an excessive response (>20 oocytes) compared with women with a normal response (10-15 oocytes): adjusted odds ratio (OR) 1.15, 95% confidence interval (CI) 1.03-1.28 for PTB, adjusted OR 1.17, 95% CI 1.05-1.30 for LBW, respectively. There was no increased risk of the adverse outcomes among women with a poor ovarian response (≤3 oocytes) compared with women with a normal response: adjusted OR0.88, 95% CI 0.76- 1.01 for PTB, adjusted OR0.92, 95% CI 0.79-1.06 for LBW, respectively. LIMITATIONS, REASONS FOR CAUTION: Although the analysis was adjusted for a number of potential confounders, the dataset had no information on other important confounders such as smoking, BMI and the medical history of women during pregnancy. Furthermore, the dataset did not allow specific identification of women with PCOS and its anonymized nature did not make it permissible to analyse one cycle per woman. WIDER IMPLICATIONS Of THE FINDINGS: Analysis of this large dataset suggests that a high oocyte number (>20) following IVF is associated with a higher risk of PTB and LBW. These findings lead to speculation whether ovarian dysfunction and/or an altered endometrial milieu resulting from supraphysiological steroid levels underlie the unfavourable outcomes and warrant further research. Ovarian stimulation regimens should optimize the number of oocytes retrieved to avoid the risk of adverse outcomes associated with very high numbers of oocytes. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained. There are no competing interests to declare. [ABSTRACT FROM AUTHOR]

المؤلفون: Barbuscia, Anna, Martikainen, Pekka, Myrskylä, Mikko, Remes, Hanna, Somigliana, Edgardo, Klemetti, Reija, Goisis, Alice

المصدر: Human Reproduction; Jan2020, Vol. 35 Issue 1, p212-220, 9p, 3 Charts, 2 Graphs

مصطلحات موضوعية: MATERNAL age, REPRODUCTIVE technology, PREMATURE labor, CHILDBIRTH, LOW birth weight, RESEARCH, PREMATURE infants, RESEARCH methodology, ACQUISITION of data, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies

مصطلحات جغرافية: FINLAND

مستخلص: Study Question: Does the risk of low birth weight and premature birth increase with age among mothers who conceive through medically assisted reproduction (MAR)?Summary Answer: Among MAR mothers, the risk of poorer birth outcomes does not increase with maternal age at birth except at very advanced maternal ages (40+).What Is Known Already: The use of MAR treatments has been increasing over the last few decades and is especially diffused among women who conceive at older ages. Although advanced maternal age is a well-known risk factor for adverse birth outcomes in natural pregnancies, only a few studies have directly analysed the maternal age gradient in birth outcomes for MAR mothers.Study Design, Size, Duration: The base dataset was a 20% random sample of households with at least one child aged 0-14 at the end of 2000, drawn from the Finnish population register and other administrative registers. This study included children who were born in 1995-2000, because the information on whether a child was conceived through MAR or naturally was available only from 1995 onwards.Participants/materials, Setting, Methods: The outcome measures were whether the child had low birth weight (LBW, <2500 g at birth) and whether the child was delivered preterm (<37 weeks of gestation). Conceptions through MAR were identified by examining data on purchases of prescription medication from the National Prescription Register. Linear probability models were used to analyse and compare the maternal age gradients in birth outcomes of mothers who conceived through MAR or naturally before and after adjustment for maternal characteristics (i.e. whether the mother suffered from acute/chronic conditions before the pregnancy, household income and whether the mother smoked during pregnancy).Main Results and the Role Of Chance: A total of 56 026 children, 2624 of whom were conceived through MAR treatments, were included in the study. Among the mothers who used MAR to conceive, maternal age was not associated with an increased risk of LBW (the overall prevalence was 12.6%) at ages 25-39. For example, compared to the risk of LBW at ages 30-34, the risk was 0.22 percentage points lower (95% CI: -3.2, 2.8) at ages 25-29 and was 1.34 percentage points lower (95% CI: -4.5, 1.0) at ages 35-39. The risk of LBW was increased only at maternal ages ≥40 (six percentage points, 95% CI: 0.2, 12). Adjustment for maternal characteristics only marginally attenuated these associations. In contrast, among the mothers who conceived naturally, the results showed a clear age gradient. For example, compared to the risk of LBW (the overall prevalence was 3.3%) at maternal ages 30-34, the risk was 1.1 percentage points higher (95% CI: 0.6, 1.6) at ages 35-39 and was 1.5 percentage points higher (95% CI: 0.5, 2.6) at ages ≥40. The results were similar for preterm births.Limitations, Reason For Caution: A limited number of confounders were included in the study because of the administrative nature of the data used. Our ability to reliably distinguish mothers based on MAR treatment type was also limited.Wider Implications Of the Findings: This is the first study to analyse the maternal age gradient in the risk of adverse birth outcomes among children conceived through MAR using data from a nationally representative sample and controlling for important maternal health and socio-economic characteristics. This topic is of considerable importance in light of the widespread and increasing use of MAR treatments.Study Funding/competing Interest(s): Funding for this project was provided by the European Research Council (grant no. 803959 MARTE to Alice Goisis and grant no. 336475 COSTPOST to Mikko Myrskylä). E.S. reports personal fees from Theramex, personal fees from Merck Serono, personal fees from Health Reimbursement Arrangement, non-financial support from Merck Serono and grants from Ferring, grants from Theramex, outside the submitted work. The remaining authors have no competing interests.Trial Registrtion Number: N/A. [ABSTRACT FROM AUTHOR]

: Copyright of Human Reproduction is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Marconi, Nicola, Raja, Edwin Amalraj, Bhattacharya, Siladitya, Maheshwari, Abha

المصدر: Human Reproduction; Sep2019, Vol. 34 Issue 9, p1716-1725, 10p, 1 Diagram, 3 Charts, 1 Graph

مصطلحات موضوعية: CHILDBIRTH, EMBRYO transfer, BIRTH weight, BODY mass index, PREMATURE labor

مصطلحات جغرافية: ITALY, UNITED Kingdom

مستخلص: Study Question: Are perinatal outcomes different between singleton live births conceived from fresh blastocyst transfer and those following the transfer of fresh cleavage-stage embryos?Summary Answer: Fresh blastocyst transfer does not increase risks of preterm birth (PTB), low/high birth weight or congenital anomaly and does not alter the sex ratio at birth or prejudice the chance of having a healthy baby.What Is Known Already: Extended embryo culture is currently considered the best option for embryo selection, but concerns have been raised about increased risks of preterm delivery and large-for-gestational-age (LGA) babies.Study Design, Size, Duration: We conducted a retrospective cohort study based on data from the Human Fertilisation and Embryology Authority (HFEA) anonymised and cycle-based dataset in the UK between 1999 and 2011.Participants/materials, Setting, Methods: Baseline characteristics were compared between in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) blastocyst-stage and cleavage-stage embryo transfer cycles using the χ2 test for categorical/dichotomised covariates and the Mann-Whitney test for continuous covariates. Statistical significance was set at <0.005. Poisson regression and multinomial logistic regression were used to establish relationships between perinatal outcomes and blastocyst-stage embryo transfer or cleavage-stage embryo transfer. Risk ratios (RRs), adjusted risk ratios (aRRs) and their 99.5% confidence intervals (CIs) were calculated as a measure of strength of associations. Results were adjusted for clinically relevant covariates. A sub-group analysis included women undergoing their first IVF/ICSI treatment. The level of significance was set at <0.05, and 95% CIs were calculated in the sub-group analysis.Main Results and the Role Of Chance: Of a total of 67 147 IVF/ICSI cycles, 11 152 involved blastocyst-stage embryo(s) and 55 995 involved cleavage-stage embryo(s). The two groups were comparable with regards to the risk of PTB (aRR, 1.00; 99.5% CI, 0.79-1.25), very-preterm birth (VPTB) (aRR, 1.00; 99.5% CI, 0.63-1.54), very-low birth weight (VLBW) (aRR, 0.84; 99.5% CI, 0.53-1.34), low birth weight (LBW) (aRR, 0.92; 99.5% CI, 0.73-1.16), high birth weight (HBW) (aRR, 0.94; 99.5% CI, 0.75-1.18) and very-high birth weight (VHBW) (aRR, 1.05; 99.5% CI, 0.66-1.65). The risk of congenital anomaly was 16% higher in the blastocyst-stage group than in the cleavage-stage group, but this was not statistically significant (aRR, 1.16; 99.5% CI, 0.90-1.49). The chance of having a healthy baby (born at term, with a normal birth weight and no congenital anomalies) was not altered by extended culture (aRR, 1.00; 99.5% CI, 0.93-1.07). Extended culture was associated with a marginal increase in the chance having a male baby in the main cycle-based analysis (aRR, 1.04; 99.5% CI, 1.01-1.09) but not in the sub-group analysis of women undergoing their first cycle of treatment (aRR, 1.04; 95% CI, 1.00-1.08). In the sub-group analysis, the risk of congenital anomalies was significantly higher after blastocyst-stage embryo transfer (aRR, 1.42; 95% CI, 1.12-1.81).Limitations, Reasons For Caution: This study is limited by the use of observational data and inability to adjust for key confounders, such as maternal smoking status and body mass index (BMI), which were not recorded in the HFEA dataset. As the main analysis was cycle-based and we were unable to link cycles within women undergoing more than one IVF/ICSI cycle, we undertook a sub-group analysis on women undergoing their first treatment cycle.Wider Implications Of the Findings: Our findings should reassure women undergoing blastocyst-stage embryo transfer. For the first time, we have shown that babies born after blastocyst transfer have a similar chance of being healthy as those born after cleavage-stage embryos transfer.Study Funding/competing Interest(s): The research activity of Dr Nicola Marconi was funded by the scholarship 'A. Griffini-J. Miglierina', Fondazione Comunitaria del Varesotto, Provincia di Varese, Italy. The authors do not have any competing interests to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

: Copyright of Human Reproduction is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Eapen, A, Joing, M, Kwon, P, Tong, J, Maneta, E, Santo, C De, Mussai, F, Lissauer, D, Carter, D, De Santo, C, RESPONSE study group

المصدر: Human Reproduction; Mar2019, Vol. 34 Issue 3, p424-432, 9p, 1 Diagram, 2 Charts, 1 Graph

مصطلحات موضوعية: RECURRENT miscarriage, CLINICAL trials, CHILDBIRTH, FIRST trimester of pregnancy, BIRTH rate, PREMATURE labor

مصطلحات جغرافية: UNITED Kingdom, UNITED States

مستخلص: Study Question: Does administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) in the first trimester improve pregnancy outcomes, among women with a history of unexplained recurrent pregnancy loss?Summary Answer: rhG-CSF administered in the first trimester of pregnancy did not improve outcomes among women with a history of unexplained recurrent pregnancy loss.What Is Known Already: The only previous randomized controlled study of granulocyte colony stimulating factor in recurrent miscarriage in 68 women with unexplained primary recurrent miscarriage found a statistically significant reduction in miscarriage and improvement in live birth rates. A further four observational studies where G-CSF was used in a recurrent miscarriage population were identified in the literature, two of which confirmed statistically significant increase in clinical pregnancy and live birth rates.Study Design, Size, Duration: A randomized, double-blind, placebo controlled clinical trial involving 150 women with a history of unexplained recurrent pregnancy loss was conducted at 21 sites with established recurrent miscarriage clinics in the United Kingdom between 23 June 2014 and 05 June 2016. The study was coordinated by University of Birmingham, UK.Participants/materials, Setting, Methods: One hundred and fifty women with a history of unexplained recurrent pregnancy loss: 76 were randomized to rhG-CSF and 74 to placebo. Daily subcutaneous injections of recombinant human granulocyte - colony stimulating factor 130 μg or identical appearing placebo from as early as three to five weeks of gestation for a maximum of 9 weeks. The trial used central randomization with allocation concealment. The primary outcome was clinical pregnancy at 20 weeks of gestation, as demonstrated by an ultrasound scan. Secondary outcomes included miscarriages, livebirth, adverse events, stillbirth, neonatal birth weight, changes in clinical laboratory variables following study drug exposure, major congenital anomalies, preterm births and incidence of anti-drug antibody formation. Analysis was by intention to treat.Main Results and the Role Of Chance: A total of 340 participants were screened for eligibility of which 150 women were randomized. 76 women (median age, 32[IQR, 29-34] years; mean BMI, 26.3[SD, 4.2]) and 74 women (median age, 31[IQR, 26-33] years; mean BMI, 25.8[SD, 4.2]) were randomized to placebo. All women were followed-up to primary outcome, and beyond to live birth. The clinical pregnancy rate at 20 weeks, as well as the live birth rate, was 59.2% (45/76) in the rhG-CSF group, and 64.9% (48/74) in the placebo group, giving a relative risk of 0.9 (95% CI: 0.7-1.2; P = 0.48). There was no evidence of a significant difference between the groups for any of the secondary outcomes. Adverse events (AEs) occurred in 52 (68.4%) participants in rhG-CSF group and 43 (58.1%) participants in the placebo group. Neonatal congenital anomalies were observed in 1/46 (2.1%) of babies in the rhG-CSF group versus 1/49 (2.0%) in the placebo group (RR of 0.9; 95% CI: 0.1-13.4; P = 0.93).Limitations, Reasons For Caution: This trial was conducted in women diagnosed with unexplained recurrent pregnancy loss and therefore no screening tests (commercially available) were performed for immune dysfunction related pregnancy failure/s.Wider Implications Of the Findings: To our knowledge, this is the first multicentre study and largest randomized clinical trial to investigate the efficacy and safety of granulocyte human colony stimulating factor in women with recurrent miscarriages. Unlike the only available single center RCT, our trial showed no significant increase in clinical pregnancy or live births with the use of rhG-CSF in the first trimester of pregnancy.Study Funding/competing Interest(s): This study was sponsored and supported by Nora Therapeutics, Inc., 530 Lytton Avenue, 2nd Floor, Palo Alto, CA 94301, USA. Darryl Carter was the co-founder and VP of research, Nora Therapeutics, Inc. and held shares in the company. He holds a patent for the use of recombinant human granulocyte colony stimulating factor to reduce unexplained recurrent pregnancy loss. Mark Joing, Paul Kwon and Jeff Tong were or are employees of Nora Therapeutics, Inc. No other potential conflict of interest relevant to this article was reported.Trial Registration Number: EUDRACT No: 2014-000084-40; ClinicalTrials.gov Identifier: NCT02156063.Trial Registration Date: 31 Mar 2014.Date Of First Patient’s Enrolment: 23 Jun 2014. [ABSTRACT FROM AUTHOR]

: Copyright of Human Reproduction is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Yi-Hua Chen¹, Herng-Ching Lin² henry11111@tmu.edu.tw, Shu-Fen Chen², Hsiu-Chen Lin³

المصدر: Human Reproduction. Dec2009, Vol. 24 Issue 12, p3049-3056. 8p. 2 Charts.

مصطلحات موضوعية: *PREMATURE labor, *CHILDBIRTH, *HIGH-risk pregnancy, *UTERINE fibroids, *PREGNANT women

مستخلص: BACKGROUND: Using a 3-year nationwide population-based database, this study examines the risk of adverse pregnancy outcomes [lower birthweight, preterm gestation and babies small for gestational age (SGA)] in pregnant women with uterine leiomyoma. [ABSTRACT FROM PUBLISHER]

المؤلفون: A.S. Khashan, R. McNamee, K.M. Abel, P.B. Mortensen, L.C. Kenny, M.G. Pedersen, R.T. Webb, P.N. Baker

المصدر: Human Reproduction. Feb2009, Vol. 24 Issue 2, p429-429. 1p.

مصطلحات موضوعية: *PREMATURE labor, *PREGNANCY complications, *PRENATAL influences, *LIFE change events, *CHILDBIRTH, *SECOND trimester of pregnancy, *REGRESSION analysis

مصطلحات جغرافية: DENMARK

مستخلص: BACKGROUND Preterm birth and other pregnancy complications have been linked to maternal stress during pregnancy. We investigated the association between maternal exposure to severe life events and risk of preterm birth. METHODS Mothers of all singleton live births (n = 1.35 million births) in Denmark between 1 January 1979 and 31 December 2002 were linked to data on their children, parents, siblings and partners. We defined exposure as death or serious illness in close relatives in the first or second trimesters or in the 6 months before conception. Log-linear binomial regression was used to estimate the effect of exposure on preterm birth, very preterm birth and extremely preterm birth. RESULTS There were 58 626 (4.34%) preterm births ( CONCLUSIONS Our population-based cohort study suggests that maternal exposure to severe life events, particularly in the 6 months before pregnancy, may increase the risk of preterm and very preterm birth. [ABSTRACT FROM AUTHOR]