Risk factors associated with preterm birth in singletons born after IVF: a national cohort study.

RESEARCH QUESTION: What are the risk factors for prematurity other than intrauterine growth restriction in singletons after IVF? DESIGN: Data were collected from a national registry, based on an observational prospective cohort of 30,737 live births after assisted reproductive technology (fresh embryo transfers: n = 20,932 and frozen embryo transfer [FET] n = 9805) between 2014 and 2015. A population of not-small for gestational age singletons conceived after fresh embryo transfers and FET, and their parents, was selected. Data on a number of variables were collected, including type of infertility, number of oocytes retrieved and vanishing twins. RESULTS: Preterm birth occurred in 7.7% (n = 1607) of fresh embryo transfers and 6.2% (n = 611) of frozen-thawed embryo transfers (P < 0.0001; adjusted odds ratio [aOR] = 1.34 [1.21-1.49]). Endometriosis and vanishing twin increased the risk of preterm birth after fresh embryo transfer (P < 0.001; aOR 1.32 and 1.78, respectively). Polycystic ovaries or more than 20 oocytes retrieved also increased preterm birth risk (aOR 1.31 and 1.30; P = 0.003 and P = 0.02, respectively); large oocyte cohort (>20) was no longer associated with the risk of prematurity in FET. CONCLUSION: Endometriosis remains a risk for prematurity even in the absence of intrauterine growth retardation, which suggests a dysimmune effect. Large oocyte cohorts obtained by stimulation, without clinical polycystic ovary syndrome diagnosed before attempts, do not affect FET outcomes, reinforcing the idea of a phenotypic difference in the clinical presentation of polycystic ovary syndrome.

Do in vitro fertilization, intrauterine insemination or female infertility impact the risk of congenital anomalies in singletons? A longitudinal national French study.

STUDY QUESTION: Do IVF, IUI or female infertility (i.e. endometriosis, polycystic ovary syndrome [PCOS] and primary ovarian insufficiency [POI]) lead to an increased risk of congenital anomalies in singletons? SUMMARY ANSWER: After multivariable adjustments, the increased risks of congenital defects associated with IUI were no longer significant, but the underlying maternal infertility presented a potential emental risk, in addition to the risk associated with IVF. WHAT IS KNOWN ALREADY: Most epidemiological studies suggest that singletons born from ART have a higher risk of birth defects, specifically musculoskeletal, cardiovascular and urogenital disorders. However, most of these studies were established on data obtained at birth or in the neonatal period and from relatively small populations or several registries. Moreover, to our knowledge, female infertility, which is a potential confounder, has never been included in the risk assessment. STUDY DESIGN, SIZE, DURATION: Using data from the French National Health System database, we conducted a comparative analysis of all singleton births (deliveries ≥22 weeks of gestation and/or >500 g of birthweight) in France over a 5-year period (2013-2017) resulting from fresh embryo or frozen embryo transfer (fresh-ET or FET from IVF/ICSI cycles), IUI and natural conception (NC). Data were available for this cohort of children at least up to early childhood (2.5 years old). PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 3 501 495 singleton births were included (3 417 089 from NC, 20 218 from IUI, 45 303 from fresh-ET and 18 885 from FET). Data were extracted from national health databases and used to identify major birth defects. Malformations were classified according to the 10th revision of the International Classification of Disease. To analyse the effect of mode of conception, multivariable analyses were performed with multiple logistic regression models adjusted for maternal age, primiparity, obesity, smoking, history of high blood pressure or diabetes and female infertility. MAIN RESULTS AND THE ROLE OF CHANCE: In our cohort of children, the overall prevalence of congenital malformations was 3.78% after NC, 4.53% after fresh-ET, 4.39% after FET and 3.91% after IUI (132 646 children with major malformations). Compared with infants conceived naturally, children born after fresh-ET and after FET had a significantly higher prevalence of malformations, with an adjusted odds ratio (aOR) of 1.15 [95% CI 1.10-1.20, P < 0.0001] and aOR of 1.13 [95% CI 1.05-1.21, P = 0.001], respectively. Among the 15 relevant subgroups of malformations studied, we observed a significantly increased risk of eight malformations in the fresh-ET group compared with the NC group (i.e. musculoskeletal, cardiac, urinary, digestive, neurological, cleft lip and/or palate and respiratory). In the FET group, this increased risk was observed for digestive and facial malformations. The overall risk of congenital malformations, and the risk by subtype, was similar in the IUI group and the NC group (overall risk: aOR of 1.01 [95% CI 0.94-1.08, P = 0.81]). In addition, there was an overall independent increase in the risk of congenital defects when the mothers were diagnosed with endometriosis (1.16 aOR [95% CI 1.10-1.22], P < 0.0001), PCOS (1.20 aOR [95% CI 1.08-1.34], P = 0.001) or POI (1.52 aOR [95% CI 1.23-1.88], P = 0.0001). Chromosomal, cardiac and neurological anomalies were more common in the three maternal infertility groups. LIMITATIONS, REASONS FOR CAUTION: Male infertility, the in vitro fertilization method (i.e. in vitro fertilization without or with sperm injection: conventional IVF vs ICSI) and embryo stage at transfer could not be taken into account. Furthermore, residual confounding cannot be excluded as well as uncertainties regarding the diagnostic criteria used for the three female infertilities. Findings for specific malformations should be interpreted with caution because the number of cases was small in some sub-groups (potentially due to the Type I error or multiple testing). WIDER IMPLICATIONS OF THE FINDINGS: In this large study, after multivariable maternal adjustments, a moderately increased risk of defects subsisted after IVF, while those associated with IUI were no longer significant. In addition, our results showed that underlying maternal infertility could contribute to the increased risk of defects associated with IVF. These novel findings highlight the importance of taking into account the ART treatment methods and the type of infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Agency of Biomedicine. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: NA.

First-trimester combined screening for trisomy 21 in women with renal disease.

OBJECTIVE: To evaluate the results of first-trimester combined screening for Down syndrome in women with chronic renal disease. METHOD: Fifty-five pregnant women with renal disease were compared with 110 patients matched for maternal age, maternal weight, smoking status, and gestational age. Maternal renal function was assayed at the time of the combined screening, and renal insufficiency was defined by serum creatinine >90 µmol/L and renal clearance <80 mL/min. We defined three groups: kidney disease and normal renal function (group 1), kidney disease and renal insufficiency (group 2), and a control group (group 3). The values of nuchal translucency, pregnancy-associated plasma protein A, human ß-chorionic gonadotrophin (hCGß), and false-positive rates for Down syndrome screening were compared. RESULTS: There were 39 (71%) and 16 (29%) cases in groups 1 and 2, respectively. Nuchal translucency and multiple of the median (MoM) pregnancy-associated plasma protein A were similar in the three groups. However, MoM hCGß levels were higher in group 2 than in groups 1 and 3 (5.37 vs 1.1 vs 0.98 MoM, p = 0.0001). The resulting screen-positive rate was also higher in group 2 than in groups 1 and 3 (43.7% vs 10.2% vs 5.5%, p = 0.0001). CONCLUSION: Trisomy 21 first-trimester screening using hCGß is not suitable in the case of maternal renal failure. © 2014 John Wiley & Sons, Ltd.

Macroporous Mannitol Granules Produced by Spray Drying and Sacrificial Templating.

In pharmaceutical applications, the porous particles of organic compounds can improve the efficiency of drug delivery, for example into the pulmonary system. We report on the successful preparation of macroporous spherical granules of mannitol using a spray-drying process using polystyrene (PS) beads of ~340 nm diameter as a sacrificial templating agent. An FDA-approved solvent (ethyl acetate) was used to dissolve the PS beads. A combination of infrared spectroscopy and thermogravimetry analysis proved the efficiency of the etching process, provided that enough PS beads were exposed at the granule surface and formed an interconnected network. Using a lab-scale spray dryer and a constant concentration of PS beads, we observed similar granule sizes (~1-3 microns) and different porosity distributions for the mannitol/PS mass ratio ranging from 10:1 to 1:2. When transferred to a pilot-scale spray dryer, the 1:1 mannitol/PS composition resulted in different distributions of granule size and porosity depending on the atomization configuration (two-fluid or rotary nozzle). In all cases, the presence of PS beads in the spray-drying feedstock was found to favor the formation of the α mannitol polymorph and to lead to a small decrease in the mannitol decomposition temperature when heating in an inert atmosphere.

Angiomyofibroblastoma: a rare vulvar tumor.

INTRODUCTION: Angiomyofibroblastoma is a rare, benign mesenchymal tumor that occurs mainly in the vulval region of middle age (35-45 years) women. CASE: We describe a 41-year-old woman, presenting with a 10-cm right vulvar mass and persistent perineal pain lasting 1 month. A surgical excision of the lesion was performed and a large mass with an intact capsule was sent for pathological examination. The results indicated angiomyofibroblastoma. CONCLUSION: The differential diagnosis between angiomyofibroblastoma (AMF) and aggressive angiomyxoma (AAM) is very important because prognoses are not the same. AMF is a well-circumscribed lesion, with a weak risk of local non-destructive recurrence. AAM is a locally aggressive and infiltrative neoplasm, with a high risk of local aggressive recurrence. Wide excision with a rim of normal tissue is recommended in all cases of vulvar tumors.

Reproductive technologies, female infertility, and the risk of imprinting-related disorders.

BACKGROUND: Epidemiological studies suggest that singletons born from assisted reproductive technologies (ART) have a high risk of adverse perinatal outcomes, specifically for imprinting disorders. Because ART processes take place at times when epigenetic reprogramming/imprinting are occurring, there is concern that ART can affect genomic imprints. However, little is currently known about the risk of imprinting defects according to the type of ART or the type of underlying female infertility. From the French national health database, a cohort of 3,501,495 singletons born over a 5-year period (2013-2017) following fresh embryo or frozen embryo transfers (fresh-ET or FET from in vitro fertilization), intrauterine insemination, or natural conception was followed up to early childhood. Based on clinical features, several syndromes/diseases involving imprinted genes were monitored. The effects of ART conception and the underlying cause of female infertility were assessed. RESULTS: Compared with infants conceived naturally, children born after fresh-ET had a higher prevalence of imprinting-related diseases, with an aOR of 1.43 [95% CI 1.13-1.81, p = 0.003]. Namely, we observed an increased risk of neonatal diabetes mellitus (1.96 aOR [95% CI 1.43-2.70], p < 0.001). There was an overall independent increase in risk of imprinting diseases for children with mothers diagnosed with endometriosis (1.38 aOR [95% CI 1.06-1.80], p = 0.02). Young and advanced maternal age, primiparity, obesity, smoking, and history of high blood pressure or diabetes were also associated with high global risk. CONCLUSIONS: This prospective epidemiological study showed that the risk of clinically diagnosed imprinting-related diseases is increased in children conceived after fresh embryo transfers or from mothers with endometriosis. The increased perturbations in genomic imprinting could be caused by controlled ovarian hyperstimulation and potentially endometriosis through the impairment of endometrial receptivity and placentation, leading to epigenetic feto-placental changes. Further studies are now needed to improve understanding of the underlying molecular mechanisms (i.e. genetic or epigenetic causes).

Acid folic and pregnancy: A mandatory supplementation.

Neural tube defects (NTD) occur in 0.5 to 2 per 1000 pregnancies with various handicaps for the affected child. It is now well established that folic acid deficiency (absolute or relative) is a predisposing factor to this type of malformation. Several randomized controlled trials showed that high-dose folic acid (4mg) is an essential factor for prevention of neural tube defects recurrence and significantly prevents the first occurrence of neural tube defects with a lower dose (0.4mg). Other etiologies can favor the occurrence of NTD such as MTHFR polymorphism, some antiepileptic therapies, obesity and pregestational mellitus diabetes. Necessity of a preconception folic acid supplementation or at least folate nutritional status evaluation should be known for all of us including patients and public.

Prevention of shoulder dystocia: A randomized controlled trial to evaluate an obstetric maneuver.

OBJECTIVE: Shoulder dystocia is a major obstetric emergency defined as a failure of delivery of the fetal shoulder(s). This study evaluated whether an obstetric maneuver, the push back maneuver performed gently on the fetal head during delivery, could reduce the risk of shoulder dystocia. STUDY DESIGN: We performed a multicenter, randomized, single-blind trial to compare the push back maneuver with usual care in parturient women at term. The primary outcome, shoulder dystocia, was considered to have occurred if, after delivery of the fetal head, any additional obstetric maneuver, beginning with the McRoberts maneuver, other than gentle downward traction and episiotomy was required. RESULTS: We randomly assigned 522 women to the push back maneuver group (group P) and 523 women to the standard vaginal delivery group (group S). Finally, 473 women assigned to group P and 472 women assigned to group S delivered vaginally. The rate of shoulder dystocia was significantly lower in group P (1·5%) than in group S (3·8%) (odds ratio [OR] 0·38 [0·16-0·92]; P = 0·03). After adjustment for predefined main risk factors, dystocia remained significantly lower in group P than in group S. There were no significant between-group differences in neonatal complications, including brachial plexus injury, clavicle fracture, hematoma and generalized asphyxia. CONCLUSION: In this trial in 945 women who delivered vaginally, the push back maneuver significantly decreased the risk of shoulder dystocia, as compared with standard vaginal delivery.

The impact of poly implant prothèse fraud on breast cancer patients: a report by the institut curie.

In March of 2010, French authorities suspended the use of breast implants made by the company Poly Implant Prothèse. Institut Curie is a large cancer center, and Poly Implant Prothèse was one major silicone-filled breast implant brand used. This report describes the impact of the fraudulent implants worldwide and more specifically on patient care at the authors' unit. From 2002 to 2009, the median number of Poly Implant Prothèse implants removed per year was 32. Since the first alert in March of 2010, 252 of these breast implants were removed in 2010 and 2011. The breast implants removed were mainly reported as normal, with a rupture rate of less than 5 percent before 2008. However, the annual rupture rate has increased from 2008 to 2011 (8, 14, 20, and 23 percent, respectively). The Institut Curie, in conjunction with breast cancer patients, has organized a management plan to deal with this major industrial fraud. Its surveillance program of breast cancer patients facilitated the management of patients during this difficult time.

Uterine artery, umbilical, and fetal cerebral Doppler velocities after epidural analgesia during labor.

OBJECTIVE: To evaluate the effects of epidural analgesia on uterine artery, umbilical, and fetal cerebral Doppler velocities during labor. METHODS: In a prospective study at Beaujon Hospital, Paris, France, between September and December 2010, uterine artery, umbilical, and fetal cerebral Doppler flow velocities were measured in 12 pregnant women during spontaneous labor with epidural analgesia. The data were registered in a period of uterine relaxation before, and 20 and 60 minutes after the first administration of epidural analgesic drugs. The changes in Doppler velocimetry values and fetal heart rate after epidural analgesia were analyzed. RESULTS: Uterine artery velocities, but neither umbilical nor fetal cerebral Doppler velocities, were decreased significantly at 20 minutes and 1 hour after epidural analgesia (P<0.005). Women with the greatest decrease in uterine artery Doppler flow velocities delivered neonates with the lowest values of umbilical artery blood pH. CONCLUSION: The data suggest that the Doppler flow velocity of uterine arteries is affected by epidural analgesia during labor. Numerous Doppler flow studies of the effect of neuraxial blockade during labor on umbilical and uterine arteries have been published with incredibly variable and inconsistent results.