Publications by authors named "Pierre-Emmanuel Bouet"

36 Publications

Delivery Mode After Manual Rotation of Occiput Posterior Fetal Positions: A Randomized Controlled Trial.

Obstet Gynecol 2021 06;137(6):999-1006

Department of Obstetrics, the Department of Biostatistics and Methodology, the Department of Neonatal Medicine, the Department of Reproductive Medicine, Angers University Hospital, and the MITOVASC Institute, CNRS 6015, INSERM U1083, Angers University, Angers, and CESP-INSERM, U1018, Team 7, Reproductive and Sexual Health, Paris-Sud University, Kremlin-Bicêtre, France.

Objective: To evaluate whether manual rotation of fetuses in occiput posterior positions at full dilation increases the rate of spontaneous vaginal delivery.

Methods: In an open, single-center, randomized controlled trial, patients with a term, singleton gestation, epidural analgesia, and ultrasonogram-confirmed occiput posterior position at the start of the second stage of labor were randomized to either manual rotation or expectant management. Our primary endpoint was the rate of spontaneous vaginal delivery. Secondary endpoints were operative vaginal delivery, cesarean delivery, and maternal and neonatal morbidity. Analyses were based on an intention-to-treat method. A sample size of 107 patients per group (n=214) was planned to detect a 20% increase in the percent of patients with a spontaneous vaginal delivery (assuming 60% without manual rotation vs 80% with manual rotation) with 90% power and alpha of 0.05.

Results: Between February 2017 and January 2020, 236 patients were randomized to either manual rotation (n=117) or expectant management (n=119). The success rate of the manual rotation maneuver, defined by conversion to an anterior position as confirmed by ultrasonogram, was 68%. The rate of the primary endpoint did not differ between the groups (58.1% in manual rotation group vs 59.7% in expectant management group (risk difference -1.6; 95% CI -14.1 to 11.0). Manual rotation did not decrease the rate of operative vaginal delivery (29.9% in manual rotation group vs 33.6% in expectant management group (risk difference -3.7; 95% CI -16.6 to 8.2) nor the rate of cesarean delivery (12.0% in manual rotation group vs 6.7% in expectant management group (risk difference 5.3; 95% CI -2.2 to 12.6). Maternal and neonatal morbidity was also similar across the two groups.

Conclusion: Manual rotation of occiput posterior positions at the start of second stage of labor does not increase the rate of vaginal delivery without instrumental assistance.

Clinical Trial Registration: ClinicalTrials.gov, NCT03009435.
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http://dx.doi.org/10.1097/AOG.0000000000004386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132900PMC
June 2021

Mitochondria: their role in spermatozoa and in male infertility.

Hum Reprod Update 2021 Feb 8. Epub 2021 Feb 8.

MITOVASC Institute, CNRS 6015, INSERM U1083, Angers University, Angers 49000, France.

Background: The best-known role of spermatozoa is to fertilize the oocyte and to transmit the paternal genome to offspring. These highly specialized cells have a unique structure consisting of all the elements absolutely necessary to each stage of fertilization and to embryonic development. Mature spermatozoa are made up of a head with the nucleus, a neck, and a flagellum that allows motility and that contains a midpiece with a mitochondrial helix. Mitochondria are central to cellular energy production but they also have various other functions. Although mitochondria are recognized as essential to spermatozoa, their exact pathophysiological role and their functioning are complex. Available literature relative to mitochondria in spermatozoa is dense and contradictory in some cases. Furthermore, mitochondria are only indirectly involved in cytoplasmic heredity as their DNA, the paternal mitochondrial DNA, is not transmitted to descendants.

Objective And Rational: This review aims to summarize available literature on mitochondria in spermatozoa, and, in particular, that with respect to humans, with the perspective of better understanding the anomalies that could be implicated in male infertility.

Search Methods: PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews pertaining to human spermatozoa and mitochondria. Searches were performed using keywords belonging to three groups: 'mitochondria' or 'mitochondrial DNA', 'spermatozoa' or 'sperm' and 'reactive oxygen species' or 'calcium' or 'apoptosis' or signaling pathways'. These keywords were combined with other relevant search phrases. References from these articles were used to obtain additional articles.

Outcomes: Mitochondria are central to the metabolism of spermatozoa and they are implicated in energy production, redox equilibrium and calcium regulation, as well as apoptotic pathways, all of which are necessary for flagellar motility, capacitation, acrosome reaction and gametic fusion. In numerous cases, alterations in one of the aforementioned functions could be linked to a decline in sperm quality and/or infertility. The link between the mitochondrial genome and the quality of spermatozoa appears to be more complex. Although the quantity of mtDNA, and the existence of large-scale deletions therein, are inversely correlated to sperm quality, the effects of mutations seem to be heterogeneous and particularly related to their pathogenicity.

Wider Implications: The importance of the role of mitochondria in reproduction, and particularly in gamete quality, has recently emerged following numerous publications. Better understanding of male infertility is of great interest in the current context where a significant decline in sperm quality has been observed.
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http://dx.doi.org/10.1093/humupd/dmab001DOI Listing
February 2021

Embryo and Its Mitochondria.

Antioxidants (Basel) 2021 Jan 20;10(2). Epub 2021 Jan 20.

MITOVASC, Angers University, INSERM 1083-CNRS 6015, IBS-CHU, 49000 Angers, France.

The mitochondria, present in almost all eukaryotic cells, produce energy but also contribute to many other essential cellular functions. One of the unique characteristics of the mitochondria is that they have their own genome, which is only maternally transmitted via highly specific mechanisms that occur during gametogenesis and embryogenesis. The mature oocyte has the highest mitochondrial DNA copy number of any cell. This high mitochondrial mass is directly correlated to the capacity of the oocyte to support the early stages of embryo development in many species. Indeed, the subtle energetic and metabolic modifications that are necessary for each of the key steps of early embryonic development rely heavily on the oocyte's mitochondrial load and activity. For example, epigenetic reprogramming depends on the metabolic cofactors produced by the mitochondrial metabolism, and the reactive oxygen species derived from the mitochondrial respiratory chain are essential for the regulation of cell signaling in the embryo. All these elements have also led scientists to consider the mitochondria as a potential biomarker of oocyte competence and embryo viability, as well as a key target for future potential therapies. However, more studies are needed to confirm these findings. This review article summarizes the past two decades of research that have led to the current understanding of mitochondrial functions in reproduction.
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http://dx.doi.org/10.3390/antiox10020139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908991PMC
January 2021

Benefits of an oocyte pickup simulation training program using a high-fidelity simulator (PickUpSim) for obstetrics and gynaecology residents: an observational survey study.

J Obstet Gynaecol 2020 Aug 18:1-6. Epub 2020 Aug 18.

Department of Obstetrics and Gynaecology, Angers University Hospital, Angers, France.

The aim of this study was to evaluate an oocyte pick-up (OPU) simulation training program for residents using the high fidelity PickUpSim (Accurate, Cesena, Italy) simulator. The authors carried out an observational study during an OPU simulation workshop. A successful scenario was defined as an oocyte retrieval rate ≥70% without any complications. Forty-six residents affiliated to 23 different French university hospitals were included, and 37/46 (80.4%) of them successfully completed the scenario with a mean time of 3.4 ± 1.1 minutes. The oocyte retrieval rate was 442/561 (78.8%). All residents found training beneficial and 41/46 (87%) were in favour of having simulation-based training programs for OPU in their reproductive medicine departments. All residents who had previous experience with OPU (11/11) recommended the use of a simulator before performing OPU. This study confirms that high-fidelity OPU simulation is a simple and efficient method for training residents.Impact statement Simulator-based training has been shown to be effective and useful for oocyte pick-up (OPU) training. All residents found the simulation program beneficial and formative, with 80% successfully completing their scenarios in a mean time of 3.4 ± 1.1 minutes. All residents who had previous experience with OPU recommended the use of a simulator before performing OPU. Prospective studies are needed to confirm the short- and long-term positive clinical impact of OPU simulation training programs.
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http://dx.doi.org/10.1080/01443615.2020.1789951DOI Listing
August 2020

Metabolomic signature of the seminal plasma in men with severe oligoasthenospermia.

Andrology 2020 11 31;8(6):1859-1866. Epub 2020 Aug 31.

Unité Mixte de Recherche MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Santé et de la Recherche Médicale (INSERM) U1083, Université d'Angers, Angers, France.

Background: Male factor is incriminated in approximately 50% of cases of infertility. The metabolomic approach has recently been used in the assessment of sperm quality and male fertility.

Materials And Methods: We analyzed the metabolomic signatures of the seminal plasma in 20 men with severe oligoasthenospermia (prewash total motile sperm count < 5.10 ) (SOA) and compared it to 20 men with normal semen parameters, with a standardized approach of targeted and quantitative metabolomics using high-performance liquid chromatography, coupled with tandem mass spectrometry, and the Biocrates Absolute IDQ p180 kit.

Results: Among the 188 metabolites analyzed, 110 were accurately measured in the seminal plasma. A robust model discriminating the two populations (Q = 55.2%) was obtained by OPLS-DA (orthogonal partial least-squares discriminant analysis), based on the drop in concentrations of 37 metabolites with a VIP (variable important for projection) greater than 1. Overall, in men with SOA, there was a significant decrease in: 17 phosphatidylcholines and four sphingomyelins; acylcarnitines, with free L-carnitine being the most discriminating metabolite; polyunsaturated fatty acids; six amino acids (glutamate, aspartate, methionine, tryptophan, proline, and alanine); and four biogenic amines (spermine, spermidine, serotonin, and alpha-aminoadipate).

Discussion: Our signature includes several metabolic changes with different impacts on the sperm quality: a change in phospholipid composition and the saturation of their fatty acids that is potentially linked to the deterioration of sperm membranes; a carnitine deficiency that can negatively impact the energy production via fatty acid oxidation and oxidative phosphorylation; and a decreased level of amino acids and biogenic amines that can lead to dysregulated metabolic and signaling pathways.

Conclusion: We provide a global overview of the metabolic defects contributing to the structural and functional alteration of spermatozoa in severe oligoasthenospermia. These findings offer new insights into the pathophysiology of male factor infertility that could help to develop future specific treatments.
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http://dx.doi.org/10.1111/andr.12882DOI Listing
November 2020

Endometriosis Lowers the Cumulative Live Birth Rates in IVF by Decreasing the Number of Embryos but Not Their Quality.

J Clin Med 2020 Aug 1;9(8). Epub 2020 Aug 1.

Reproductive Biology Unit, Angers University Hospital, 49000 Angers, France.

Endometriosis and infertility are closely linked, but the underlying mechanisms are still poorly understood. This study aimed to evaluate the impact of endometriosis on in vitro fertilization (IVF) parameters, especially on embryo quality and IVF outcomes. A total of 1124 cycles with intracytoplasmic sperm injection were retrospectively evaluated, including 155 cycles with endometriosis and 969 cycles without endometriosis. Women with endometriosis had significantly lower ovarian reserve markers (AMH and AFC), regardless of previous ovarian surgery. Despite receiving significantly higher doses of exogenous gonadotropins, they had significantly fewer oocytes, mature oocytes, embryos, and top-quality embryos than women in the control group. Multivariate analysis did not reveal any association between endometriosis and the proportion of top-quality embryo (OR = 0.87; 95% CI [0.66-1.12]; = 0.3). The implantation rate and the live birth rate per cycle were comparable between the two groups ( = 0.05), but the cumulative live births rate was significantly lower in in the endometriosis group (32.1% versus 50.7%, = 0.001), as a consequence of the lower number of frozen embryos. In conclusion, endometriosis lowers the cumulative live birth rates by decreasing the number of embryos available to transfer, but not their quality.
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http://dx.doi.org/10.3390/jcm9082478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464781PMC
August 2020

Conversion of in vitro fertilization cycles to intrauterine inseminations in patients with a poor ovarian response: Risk of multiple pregnancies.

J Gynecol Obstet Hum Reprod 2020 Oct 11;49(8):101831. Epub 2020 Jun 11.

Department of Reproductive Medicine, Angers University Hospital, Angers, France. Electronic address:

Purpose: To determine the risk of multiple pregnancies (MP) following conversion of in vitro fertilization (IVF) cycles to intrauterine insemination (IUI) when a poor ovarian response (POR) is diagnosed during controlled ovarian stimulation (COS).

Methods: We undertook a retrospective study in our teaching hospital from January 2012 to December 2017. We included all IVF cycles with POR that were converted to IUI (<5 follicles ≥ 14 mm and peak estradiol level < 1000 pg/mL on trigger day).

Results: Overall, 205 IVF cycles that were converted to IUI in 128 patients were analyzed. Mean age was 34.1 ± 4.6 years, mean antral follicle count was 11 ± 5.3 and mean AMH was 1.8 ± 2.9 ng/L. The main causes of infertility were unexplained (41 %) (84/205) and diminished ovarian reserve (35 %) (72/205). Of all the cycles converted to IUI, 53 (26 %) had one mature follicle on trigger day, 56 (27 %) had 2, 56 (27 %) had 3, and 40 (20 %) had 4. The live birth rate (LBR) was 7.3 % (15/205), and the miscarriage rate was 28.6 % (6/21). There were 3 twin pregnancies, but no higher order pregnancies; the MP rate was 14.3 % (3/21). There was no significant difference in the MP rate between patients with 1-2 mature follicles and patients with 3-4 mature follicles (18.2 % vs 10 %, p = 0.99, respectively).

Conclusion: In IVF cycles converted to IUI for poor response, the risk of MP is acceptable (14 %) with no higher order pregnancies, even with 3 or 4 follicles ≥14 mm on trigger day.
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http://dx.doi.org/10.1016/j.jogoh.2020.101831DOI Listing
October 2020

Elevated Levels of Monocyte Chemotactic Protein-1 in the Follicular Fluid Reveals Different Populations among Women with Severe Endometriosis.

J Clin Med 2020 May 1;9(5). Epub 2020 May 1.

Unité Mixte de Recherche MITOVASC, équipe Mitolab, Centre National de la Recherche Scientifique 6015, Institut National de la Santé et de la Recherche Médicale U1083, Université d'Angers, 49000 Angers, France.

To determine if a modification of the cytokine profile occurs in the follicular fluid (FF) of women with endometriosis undergoing in vitro fertilization (IVF), we performed a prospective observational study from January 2018 to February 2019. In total, 87 women undergoing IVF were included: 43 for severe endometriosis-related infertility and 40 controls with other causes of infertility. The cytokine profile of the FF was determined by multiplex fluorescent-bead-based technology allowing the measurement of 59 cytokines. Monocyte Chemoattractant Protein 1 (MCP-1) was the only variable retained in the multivariate analysis. We identified two subgroups of patients in the endometriosis group: MCP-1-low group ( = 23), which had FF MCP-1 levels comparable to the control group, and MCP-1-high ( = 20), which had significantly higher FF levels. Only patients in the MCP-1-high group had a significantly altered cytokine profile in the FF, and had a significantly higher serum estradiol level ( = 0.002) and a significantly lower number of oocytes recovered ( = 0.01) compared to the MCP-1-low and the control group. Our study has shown an alteration of the oocyte microenvironment in women with endometriosis associated with high follicular fluid levels of MCP-1, allowing the identification of a subgroup of endometriosis patients with a potentially worse prognosis.
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http://dx.doi.org/10.3390/jcm9051306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291127PMC
May 2020

The cytokine profile of follicular fluid changes during ovarian ageing.

J Gynecol Obstet Hum Reprod 2020 Apr 3;49(4):101704. Epub 2020 Feb 3.

Reproductive Biology Unit, Angers University Hospital, 49000, Angers, France; MITOVASC Institute, CNRS 6015, INSERM U1083, Angers University, 49000, Angers, France.

Objective: Ovarian ageing is one of the commonest causes of infertility in patients consulting for assisted reproductive technology. The composition of the follicular fluid (FF), which reflects the exchanges between the oocyte and its microenvironment, has been extensively investigated to determine the metabolic pathways involved in various ovarian disorders. Considering the importance of cytokines in folliculogenesis, we focused on the cytokine profile of the FF during ovarian ageing.

Material And Methods: Our cross-sectional study assesses the levels of 27 cytokines and growth factors in the FF of two groups of women undergoing in vitro fertilization. One group included 28 patients with ovarian ageing clinically characterized by a diminished ovarian reserve (DOR), and the other group included 29 patients with a normal ovarian reserve (NOR), serving as controls.

Results: With univariate analysis, the cytokine profile was found to differ significantly between the two groups. After adjustment of the p-values, platelet-derived growth factor-BB (PDGF-BB) was the only cytokine with a significantly lower concentration in the DOR group (7.34 ± 16.11 pg/mL) than in the NOR group (24.39 ± 41.38 pg/mL) (p = 0.005), independently of chronological age.

Conclusion: Thus, PDGF-BB would seem to be implicated in the physiopathology of DOR, potentially in relation to its role in folliculogenesis or in the protection against oxidative stress.
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http://dx.doi.org/10.1016/j.jogoh.2020.101704DOI Listing
April 2020

Endometrial preparation for frozen-thawed embryo transfer in an artificial cycle: transdermal versus vaginal estrogen.

Sci Rep 2020 01 22;10(1):985. Epub 2020 Jan 22.

Department of Reproductive Medicine, Angers University Hospital, 4 rue Larrey, 49100, Angers, France.

The objective was to compare the endometrial thickness (ET) in a frozen embryo transfer (FET) cycle between transdermal and vaginal estrogen. Our secondary objectives were to compare the patient satisfaction and the pregnancy outcomes. Prospective monocentric cohort study between 01/2017 and 12/2017 at a single institution. Choice of administration was left to the patient. 119 cycles had transdermal estrogen (T-group) and 199 had vaginal estrogen (V-group). The ET at 10 ± 1 days of treatment was significantly higher in the T-group compared to the V-group (9.9 vs 9.3 mm, p = 0.03). In the T-group, the mean duration of treatment was shorter (13.6 vs 15.5 days, p < 0.001). The rate of cycle cancelation was comparable between the two groups (12.6% vs 8.5%, p = 0.24). Serum estradiol levels were significantly lower (268 vs 1332 pg/ml, p < 0.001), and serum LH levels were significantly higher (12.1 ± 16.5 vs 5 ± 7.5 mIU/ml, p < 0.001) in the T-group. Patient satisfaction was higher in the T-group (p = 0.04) and 85.7% (36/42) of women who had received both treatments preferred the transdermal over the vaginal route. Live birth rates were comparable between the two groups (18% vs 19%, p = 0.1). Transdermal estrogen in artificial FET cycles was associated with higher ET, shorter treatment duration and better tolerance.
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http://dx.doi.org/10.1038/s41598-020-57730-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976623PMC
January 2020

Metabolomics shows no impairment of the microenvironment of the cumulus-oocyte complex in women with isolated endometriosis.

Reprod Biomed Online 2019 Dec 12;39(6):885-892. Epub 2019 Aug 12.

Department of Reproductive Medicine, Angers University Hospital, Angers 49000, France; MITOVASC Institute, CNRS 6015, INSERM U1083, Angers University, Angers 49000, France; Reproductive Biology Unit, Angers University Hospital, Angers 49000, France.

Research Question: Is there any metabolomic evidence of impairment of the cumulus-oocyte complex (COC) microenvironment in the follicular fluid of women with endometriosis?

Design: A prospective observational study from January to July 2018 at the Angers University Hospital, France. Seventy-nine women undergoing IVF with or without intracytoplasmic sperm injection (ICSI) were included: 39 for endometriosis-related infertility and 40 controls with other causes of infertility. A targeted quantitative metabolomic and lipidomic analysis was performed.

Results: Patient characteristics (age, body mass index, smoking status, hormonal profile and ovarian reserve markers) were comparable between the endometriosis and the control groups. There was no significant difference in the cumulative FSH dose used for stimulation between the endometriosis and the control groups (2732 versus 2257 IU, respectively). There were no differences in the oocyte maturity rates (72.2% versus 77.7%), or in the fertilization rates in IVF and ICSI (49.4% versus 50.2% and 76.4% versus 68.8%, respectively) between the endometriosis and control groups. Among the 188 metabolites analysed, 150 were accurately measured. Univariate analysis did not reveal any significant modification of metabolite concentrations, and none of the multivariate models discriminated between the two groups of patients, even when the study was restricted to the most severe form of endometriosis.

Conclusions: No specific metabolomic signature of endometriosis was found in the follicular fluid of women undergoing IVF. These results suggest that there is no microenvironmental impairment of the COC in cases of isolated endometriosis among women with infertility.
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http://dx.doi.org/10.1016/j.rbmo.2019.08.001DOI Listing
December 2019

A mathematical model to predict mean time to delivery following cervical ripening with dinoprostone vaginal insert.

Sci Rep 2019 07 9;9(1):9910. Epub 2019 Jul 9.

Department of Obstetrics and Gynecology, Angers University Hospital, Angers, France.

The main objective of our study was to analyze the mean time to delivery following cervical ripening with a 10 mg dinoprostone vaginal insert. We performed a retrospective observational study at the level III maternity ward of Angers university hospital. We included all women who had cervical ripening with dinoprostone between January 1, 2015 and September 30, 2016. Overall, 405 patients were included, and 59.3% (240/405) were nulliparous. The mean time to delivery was 20h39 min ± 10h49 min. 21% of deliveries (86/405) occurred between midnight and 6 h a.m., and the cesarean section rate was 33% (132/405). Multiple regression analysis showed that nulliparity, overweight (BMI ≥ 25), a closed cervix on initial examination and the absence of premature rupture of membranes (PRM) all significantly increased the mean time to delivery. We developed a mathematical model integrating the aforementioned factors and their impact to help predict the mean time to delivery following cervical ripening with dinoprostone vaginal insert: Y = 961.188-80.346 × parity + 21.437 × BMI-165.263 × cervical dilation-241.759 × PRM. This equation allows obstetricians to calculate a personalized time to delivery for each patient, allowing a precise scheduling of dinoprostone insert placement, and thus improving the organization in busy maternity wards.
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http://dx.doi.org/10.1038/s41598-019-46101-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616328PMC
July 2019

Surgical treatment of postpartum haemorrhage: national survey of French residents of obstetrics and gynecology.

BMC Pregnancy Childbirth 2019 Mar 13;19(1):91. Epub 2019 Mar 13.

Department of Obstetrics and Gynecology, Bordeaux University Hospital, Bordeaux, France.

Background: Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and one of the leading causes of maternal mortality worldwide. Many medical treatments and interventions are available nowadays, but surgical treatment is sometimes required when less invasive methods are unsuccessful. This study aimed to assess the theoretical and practical knowledge of French residents of Obstetrics and Gynecology concerning the surgical treatment of postpartum haemorrhage.

Study Design: We performed a questionnaire study for senior residents of Obstetrics and Gynecology in France (fourth and fifth year of training). An anonymous survey was sent by email. Between December 2013 and April 2014, a total of 370 residents responded.

Result: The response rate was 47.6% (176/370). Only 156 questionnaires were fully completed and included for analysis. In all, 74% (115/156) of residents reported not mastering sufficiently or at all the technique for bilateral ligation of uterine arteries, 79% (123/156) for uterine compression sutures, 95% (148/156) for ligation of the internal iliac arteries, and 78% (122/156) for emergency peripartum hysterectomy. More than half of respondents (55%, 86/156) stated that they had not mastered any of these techniques.

Conclusion: An alarmingly high number of French senior residents in Obstetrics and Gynecology report that they have not acquired the sufficient surgical skills during their training to be able to perform the surgeries required for the management of PPH.
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http://dx.doi.org/10.1186/s12884-019-2237-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415489PMC
March 2019

Impact of mode of conception on neonatal and neurodevelopmental outcomes in preterm infants.

Hum Reprod 2019 02;34(2):356-364

Department of Neonatal Medicine, Angers University Hospital, Angers, France.

Study Question: Is assisted conception associated with neonatal morbidity and mortality and with neurodevelopmental impairment at 2 years of corrected age in preterm infants born before 34 weeks of gestational age?

Summary Answer: Assisted conception is not associated with an increase in neonatal morbidity and mortality and is even significantly associated with a better 2-year neurodevelopmental outcome in preterm infants.

What Is Known Already: Assisted conception appears to increase the rate of preterm births, though few studies have analysed outcomes for these preterm infants.

Study Design, Size, Duration: This prospective observational study included 703 preterm infants born between January 2009 and December 2013 and 573 of them were assessed at 2 years of corrected age.

Participants/materials, Setting, Methods: All infants born alive between 24+0 and 33+6 weeks of gestational age and hospitalised at the Angers University Hospital were eligible as long as the mode of conception was known for neonatal outcome assessment. They were enroled in the Loire Infant Follow-up Team (LIFT) prospective longitudinal cohort and included for neurodevelopmental outcome assessment. Neonatal morbidity and mortality were evaluated during hospitalisation based on a composite score including death, intraventricular haemorrhage Grade ≥3, periventricular leukomalacia, treated patent ductus arteriosus and bronchopulmonary dysplasia at 36 weeks of gestational age. The neurodevelopmental outcome at 2 years of corrected age was determined by a physical examination, a neuropsychological test and a parental questionnaire. In order to ensure comparability, infants were matched 1:1 according to maternal age, twin status and propensity score,calculated from variables usually associated (positively or negatively) with assisted conception, including gestational age, z-score of birth weight, antenatal corticosteroids and magnesium sulphate treatments, gender, parity, maternal body mass index, tobacco consumption, outborn delivery (i.e. not at a tertiary-care medical centre) and maternal socio-economic status.

Main Results And The Role Of Chance: There were 703 preterm infants included in the analysis of neonatal morbidity and mortality, including 137 born after assisted conception. After matching, 184 preterm infants were included for neonatal morbidity and mortality analysis. There was no significant association between assisted conception and neonatal morbidity and mortality (aOR 0.67, 95% CI [0.25, 1.77], P = 0.422). 573 infants were assessed at 2 years, including 121 born after assisted conception. After matching, 154 preterm infants were included for neurodevelopmental outcome analysis. Assisted conception was significantly associated with a reduction in the probability of non-optimal neurological development at 2 years (aOR 0.26, 95% CI [0.09, 0.80], P = 0.019).

Limitation, Reasons For Caution: Further studies remain necessary to fully confirm these results. This was a monocentric study and 14% of enroled infants were lost to follow up at 2 years of corrected age.

Wider Implications Of The Findings: These findings are relevant for providing appropriate information to parents considering assisted conception, and more importantly for those with a preterm infant following a pregnancy achieved by assisted conception.

Study Funding/competing Interest(s): The authors report external funding and no conflicts of interest for this work.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/dey345DOI Listing
February 2019

ConFIRM trial - conversion of in vitro fertilization cycles to intrauterine inseminations in patients with a poor ovarian response to stimulation: a protocol for a multicentric, prospective randomized trial.

Trials 2018 Oct 17;19(1):565. Epub 2018 Oct 17.

Department of Reproductive Medicine, Angers University Hospital, 4 rue Larrey, 49000, Angers, France.

Background: To date, there is no consensus on the ideal management strategy of patients with poor ovarian response (POR) to controlled ovarian stimulation (COS) for in vitro fertilization (IVF). Currently, these patients are given the choice of: (1) canceling the cycle; (2) proceeding with COS regardless of the poor response, and performing the oocyte retrieval and transfer of embryos when available; or (3) conversion to an intrauterine insemination (IUI). When the decision to proceed with the COS cycle is taken, it is not clear whether IVF or conversion to IUI is the best choice. If live birth rates were comparable between the two strategies, conversion to IUI would be the better option for poor responders, since it is less invasive and is associated with a lower cost.

Methods: We designed a non-inferiority, multicentric, randomized controlled trial that will be conducted in 18 French Reproductive Medicine centers. We defined POR as the presence of only two or four mature follicles ≥ 14 mm on ovulation trigger day. Patients with POR will be randomized into two parallel arms: "IVF" and "conversion to IUI." Our main objective is to compare the efficiency of IVF and conversion to IUI in patients with POR to COS. The primary outcome is the live birth rate, defined as the birth of a living infant after 22 weeks' gestational age, or weighing ≥ 500 g. One of the secondary objectives is to compare the cost-efficiency of both strategies at 12 months. We will need to include 940 patients (470 in each arm), and the duration of the inclusion period is estimated to be 36 months.

Discussion: This is the first randomized controlled trial to compare the outcomes of IVF and embryo transfer to conversion to IUI in patients with POR to COS. If our study shows that conversion to IUI is non-inferior to IVF in terms of clinical efficiency and live birth rate, it would confirm IUI as a better alternative for patients, both individually (less invasive and more patient-friendly) and collectively (lower cost).

Trials Registration: ClinicalTrials.gov, ID: NCT03362489 . Registered on January 10th, 2018.
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http://dx.doi.org/10.1186/s13063-018-2936-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192099PMC
October 2018

Giant condyloma acuminatum of the vulva: Successful management with imiquimod.

JAAD Case Rep 2018 Aug 15;4(7):692-694. Epub 2018 Aug 15.

Department of Obstetrics and Gynecology, Angers University Hospital, Angers, France.

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http://dx.doi.org/10.1016/j.jdcr.2018.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098202PMC
August 2018

Timing therapeutic donor inseminations in natural cycles: human chorionic gonadotrophin administration versus urinary LH monitoring.

Reprod Biomed Online 2017 Aug 18;35(2):174-179. Epub 2017 May 18.

Department of Obstetrics and Gynecology, University of Montreal, Montreal, Quebec, Canada; Department of Reproductive Medicine, Ovo Clinic, Montreal, Quebec, Canada; Department of Obstetrics and Gynecology, Angers University Hospital, Angers, France.

This cohort study assessed whether timing therapeutic donor sperm inseminations (TDI) in natural cycles (NC) using ultrasound monitoring and ovulation trigger with human chorionic gonadotrophin (US/HCG) improves cumulative live birth rates (LBR) compared with detection of LH surge with urinary kits (u-LH). It included 232 normo-ovulatory women aged ≤40 years, undergoing 538 TDI in NC between 2011 and 2014. In the u-LH group (113 women, 267 cycles), TDI was performed the day following a positive test. In the US/HCG group (119 women, 271 cycles), ovulation was triggered with HCG when a follicle ≥17 mm was noted, and TDI performed 36 h later. The first three cycles were analysed per patient. Groups were comparable for baseline characteristics. Cumulative LBR were comparable between u-LH and US/HCG groups (31.47% versus 23.11%, respectively) (log-rank test). A generalized estimating equation analysis was performed to compare outcomes per cycle. The LBR per started cycle was comparable between the u-LH and US/HCG groups (12.4% versus 9.2%, respectively). Cancellation rate was significantly higher with u-LH (19.1% versus 11.4%, P = 0.011), but did not impact overall outcomes. In conclusion, urinary LH monitoring is as effective as ultrasound monitoring and ovulation trigger with HCG in TDI performed in NC.
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http://dx.doi.org/10.1016/j.rbmo.2017.05.005DOI Listing
August 2017

Recurrent pregnancy loss: current perspectives.

Int J Womens Health 2017 17;9:331-345. Epub 2017 May 17.

Department of Obstetrics and Gynecology, Angers University Hopsital, Angers, France.

Recurrent pregnancy loss is an important reproductive health issue, affecting 2%-5% of couples. Common established causes include uterine anomalies, antiphospholipid syndrome, hormonal and metabolic disorders, and cytogenetic abnormalities. Other etiologies have been proposed but are still considered controversial, such as chronic endometritis, inherited thrombophilias, luteal phase deficiency, and high sperm DNA fragmentation levels. Over the years, evidence-based treatments such as surgical correction of uterine anomalies or aspirin and heparin for antiphospholipid syndrome have improved the outcomes for couples with recurrent pregnancy loss. However, almost half of the cases remain unexplained and are empirically treated using progesterone supplementation, anticoagulation, and/or immunomodulatory treatments. Regardless of the cause, the long-term prognosis of couples with recurrent pregnancy loss is good, and most eventually achieve a healthy live birth. However, multiple pregnancy losses can have a significant psychological toll on affected couples, and many efforts are being made to improve treatments and decrease the time needed to achieve a successful pregnancy. This article reviews the established and controversial etiologies, and the recommended therapeutic strategies, with a special focus on unexplained recurrent pregnancy losses and the empiric treatments used nowadays. It also discusses the current role of preimplantation genetic testing in the management of recurrent pregnancy loss.
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http://dx.doi.org/10.2147/IJWH.S100817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440030PMC
May 2017

Pathological postpartum period – Maternal pathology within 40 days

Rev Prat 2017 Mar;67(3):e125-128

Service de gynécologie-obstétrique, Centre hospitalier universitaire d’Angers, 49033 Angers Cedex 01, France

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March 2017

Uterine Rupture with Protruded Legs in a Large Amniocele.

N Engl J Med 2016 Dec;375(25):e51

Centre Hospitalier Universitaire d'Angers, Angers, France

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http://dx.doi.org/10.1056/NEJMicm1603843DOI Listing
December 2016

Clomiphene Citrate versus Letrozole for Ovarian Stimulation in Therapeutic Donor Sperm Insemination.

Gynecol Obstet Invest 2017 17;82(5):481-486. Epub 2016 Nov 17.

Department of Reproductive Medicine, Ovo Clinic, University of Montreal, Montreal, Que., Canada.

Aim: To compare clomiphene citrate (CC) and letrozole for ovarian stimulation (OS) in therapeutic donor sperm insemination (TDI) cycles.

Methods: Retrospective cohort study between January 2011 and June 2014 at a University-affiliated private IVF clinic in Montreal, Canada. 257 normo-ovulatory women ≤40 years of age with no history of infertility undergoing 590 TDI cycles in the absence of a male partner (single women and same-sex couples) or azoospermia were included. Patients received 100 mg CC daily (145 women, 321 cycles) or letrozole 5 mg daily (112 women, 269 cycles), from days 3 to 7. Only the first 3 cycles were included per patient. Our main outcome measure was cumulative live birth rates (LBR).

Results: Baseline characteristics were comparable between the 2 groups. There were no differences in LBR per cycle (16.5% (53/321) vs. 11.5% (31/269), p = 0.08) and cumulative LBR (36.6% (53/145) vs. 27.7% (31/112), p = 0.13), between CC and letrozole, respectively. Multiple pregnancy rate (11.6% (8/69) vs. 8.7% (4/46), p = 0.6) and miscarriage rate (21.7 vs. 21.7%, p = 1) were also comparable between CC and letrozole, respectively.

Conclusion: In normo-ovulatory women undergoing TDI, OS with CC or letrozole resulted in similar live birth and twin pregnancy rates.
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http://dx.doi.org/10.1159/000452665DOI Listing
June 2018

Fertility and Pregnancy in Turner Syndrome.

J Obstet Gynaecol Can 2016 08 23;38(8):712-8. Epub 2016 Apr 23.

Department of Reproductive Medicine, Montreal University Hospital, Montreal QC; Ovo Clinic, Montreal QC.

Turner syndrome (TS) occurs in one in 2500 live female births and is one of the most common chromosomal abnormalities in women. Pregnancies in women with TS, conceived with either autologous or donated oocytes, are considered high risk because of the associated miscarriages and life-threatening cardiovascular complications (aortic dissection, severe hypertension). Therefore, it is imperative to conduct a full preconception evaluation and counselling that includes cardiac assessment with Holter blood pressure monitoring, echocardiography, and thoracic MRI. Abnormal findings, such an aortic dilatation, mandate close monitoring throughout the pregnancy and the immediate postpartum period and could possibly contraindicate pregnancy. When in vitro fertilization using donated oocytes is performed in these women, only a single embryo should be transferred. Women with a Turner mosaic karyotype appear to have a lower risk of obstetrical and cardiovascular complications but should nevertheless undergo the full preconception evaluation. In this article, we offer guidelines on the management of women with TS in the preconception period, during pregnancy, and postpartum.
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http://dx.doi.org/10.1016/j.jogc.2016.02.007DOI Listing
August 2016

Surgical management of postpartum haemorrhage: survey of French obstetricians.

Sci Rep 2016 07 27;6:30342. Epub 2016 Jul 27.

Department of Obstetrics and Gynecology, Bordeaux University Hospital-Bordeaux, France.

The aim of our study was to assess the theoretical and practical knowledge of French obstetricians about the surgical management of postpartum haemorrhage (PPH). Our study is a national anonymous self-administered survey. A total of 363 obstetricians responded to this questionnaire between December 2013 and April 2014. Questionnaire sent through email to all French obstetricians who are members of either of two federations of hospital-based obstetricians. Answers were collected until the end of June 2014. The main outcome measure was obstetricians' level of mastery of each surgical technique. The results were analysed descriptively (proportions). Only the 286 questionnaires fully completed were analysed; the complete response rate was 23% (286/1246). In all, 33% (95/286) of the responding obstetricians reported that they had not mastered sufficiently or even at all the technique for bilateral ligation of the uterine arteries, 37% (105/286) for uterine compression suture, 62% (178/286) for ligation of the internal iliac arteries, and 47% (134/286) for emergency peripartum hysterectomy. In all, 18% (52/286) of respondents stated that they had not mastered any of these techniques. Our study shows that a worrisome number of French obstetricians reported insufficient mastery of the surgical techniques for PPH management.
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http://dx.doi.org/10.1038/srep30342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962082PMC
July 2016

Chronic endometritis in women with recurrent pregnancy loss and recurrent implantation failure: prevalence and role of office hysteroscopy and immunohistochemistry in diagnosis.

Fertil Steril 2016 Jan 9;105(1):106-10. Epub 2015 Oct 9.

Department of Reproductive Medicine, Ovo Clinic, Montreal, Quebec, Canada; Department of Obstetrics and Gynecology, University of Montreal, Montreal, Quebec, Canada.

Objective: To determine the prevalence of chronic endometritis (CE) in patients with recurrent implantation failure (RIF) after IVF and unexplained recurrent pregnancy loss (RPL).

Design: Prospective observational study between November 2012 and March 2015.

Setting: University-affiliated private IVF clinic.

Patient(s): Women with RIF after IVF (group 1) and unexplained RPL (group 2).

Intervention(s): Office hysteroscopy followed by an endometrial biopsy was performed as part of the workup for RIF and RPL. The diagnosis of CE was histologically confirmed using immunohistochemistry stains for syndecan-1 (CD138).

Main Outcome Measure(s): The prevalence of CE in each group and the sensitivity/specificity of office hysteroscopy in the diagnosis of CE.

Result(s): Ninety-nine patients were included (46 in group 1 and 53 in group 2). The mean age was 36.3 ± 4.9 years in group 1 and 34.5 ± 4.9 years in group 2. Five biopsies were uninterpretable (three in group 1 and two in group 2) because of insufficient specimen. The prevalence of CE was 14% (6/43) in group 1 and 27% (14/51) in group 2. The sensitivity and specificity of office hysteroscopy in the diagnosis of CE were 40% (8/20) and 80% (59/74), respectively.

Conclusion(s): We found a high prevalence of immunohistochemically confirmed CE in women with RIF and RPL. Office hysteroscopy is a useful diagnostic tool but should be complemented by an endometrial biopsy for the diagnosis of CE.

Clinical Trial Registration No: NCT01762098.
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http://dx.doi.org/10.1016/j.fertnstert.2015.09.025DOI Listing
January 2016

Implementation of an antenatal magnesium sulfate protocol for fetal neuroprotection in preterm infants.

Sci Rep 2015 Sep 29;5:14732. Epub 2015 Sep 29.

Department of Obstetrics and Gynecology, Bordeaux University Hospital-Bordeaux-France.

The aim of our study was to assess the feasibility of implementing a protocol for the use of magnesium sulfate to prevent cerebral palsy. This retrospective single-center study included all women with fetuses of gestational age <33 weeks of gestation whose birth was planned or expected within 24 hours from September 2011 to December 2012. They were to receive magnesium sulfate, administered intravenously as a 4-g bolus followed by a constant infusion of 1 g per hour. If delivery had not occurred after 12 hours and was no longer considered imminent, the infusion was to be discontinued. The study included 119 women, 81 (68.1%) of whom received magnesium sulfate. Among the latter, 71 (87.5%) gave birth within 24 hours. The reasons treatment was not given were: omission by medical team (19/38, 50%), urgent delivery (18/38, 47.4%), and contraindication to treatment (1/38, 2.6%). The mean gestational age at protocol implementation was 29.6 +/- 2.1 weeks. Maternal monitoring, especially at the onset of infusion, appeared suboptimal. No major maternal side effects were observed. Our study shows that implementing a protocol for prevention of cerebral palsy by magnesium sulfate is feasible in a tertiary obstetric center.
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http://dx.doi.org/10.1038/srep14732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586759PMC
September 2015

Maternal and Neonatal Morbidity After Attempted Operative Vaginal Delivery According to Fetal Head Station.

Obstet Gynecol 2015 Sep;126(3):521-529

Departments of Obstetrics and Gynecology, General Hospital, La Roche sur Yon, and Rennes University Hospital, Rennes, and the Clinical Research Center and the Department of Obstetrics and Gynecology, Angers University Hospital, Angers, France; and the Department of Obstetrics and Gynecology, St. Luc Hospital University of Montreal, Montreal, Quebec, Canada.

Objective: To compare severe short-term maternal and neonatal morbidity associated with midpelvic and low pelvic attempted operative vaginal delivery.

Methods: Prospective study of 2,138 women with live singleton term fetuses in vertex presentation who underwent an attempted operative vaginal delivery in a tertiary care university hospital. We used multivariate logistic regression and propensity score methods to compare outcomes associated with midpelvic and low pelvic delivery. Severe maternal morbidity was defined as third- or fourth-degree perineal laceration, perineal hematoma, cervical laceration, extended uterine incision for cesarean delivery, postpartum hemorrhage greater than 1,500 mL, surgical hemostatic procedures, uterine artery embolization, blood transfusion, infection, thromboembolic events, admission to the intensive care unit, and maternal death; severe neonatal morbidity was defined as 5-minute Apgar score less than 7, umbilical artery pH less than 7.00, need for resuscitation or intubation, neonatal trauma, intraventricular hemorrhage greater than grade 2, neonatal intensive care unit admission for more than 24 hours, convulsions, sepsis, and neonatal death.

Results: From December 2008 through October 2013 there were 2,138 attempted operative vaginal deliveries; 18.3% (n=391) were midpelvic, 72.5% (n=1,550) low, and 9.2% (n=197) outlet. Severe maternal morbidity occurred in 10.2% (n=40) of midpelvic, 7.8% (n=121) of low, and 6.6% (n=13) of outlet attempts (P=.21); and severe neonatal morbidity in 15.1% (n=59), 10.2% (n=158), and 10.7% (n=21) (P=.02), respectively. Multivariable logistic regression analysis found no significant difference between midpelvic and low attempted operative vaginal delivery for either composite severe maternal (adjusted odds ratio [OR] 1.01, 95% confidence interval [CI] 0.66-1.55) or neonatal morbidity (adjusted OR 1.25, 95% CI 0.84-1.86). Similarly, propensity score matching found no significant difference between midpelvic and low operative vaginal delivery for either severe maternal (adjusted OR 0.69, 95% CI 0.39-1.22) or neonatal morbidity (adjusted OR 0.88, 95% CI 0.53-1.45).

Conclusion: In singleton term pregnancies, midpelvic attempted operative vaginal delivery compared with low pelvic attempted operative vaginal delivery was not associated with an increase in severe short-term maternal or neonatal morbidity.

Level Of Evidence: II.
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http://dx.doi.org/10.1097/AOG.0000000000001000DOI Listing
September 2015

Policy of high-dose tranexamic acid for treating postpartum hemorrhage after vaginal delivery.

J Matern Fetal Neonatal Med 2016 29;29(10):1617-22. Epub 2015 Jun 29.

a Department of Obstetrics and Gynecology , Angers University Hospital , Angers , France.

Objective: To assess whether a policy of routine administration of high-dose tranexamic acid (TA) at the diagnosis of postpartum hemorrhage (PPH) reduces blood loss after vaginal birth.

Methods: This controlled single-center before-and-after study of all women with PPH ≥ 500 ml after vaginal birth took place from January 2011 through March 2012; the control group included those seen from January 2011 through August 2011, and the case patients those from September 2011 through March 2012. Our protocol for the management of PPH was modified effective September 2011 to include administration of high-dose TA (4 g of TA intravenously then 1 g/h for 6 h) once blood loss reached 800 ml. Our primary objective was to assess the efficacy of this policy in reducing blood loss in PPH.

Results: Maternal characteristics did not differ between the two groups. Mean estimated blood loss was not significantly lower in the TA group (n = 138) than in the control group (n = 151) (respectively, 915.7 ± 321 ml versus 944.8 ± 313.8 ml; p = 0.47). The difference between pre- and post-delivery hemoglobin levels were lower in the TA group (-2.6 g/dl ± 1.2 versus -2.9 g/dl ± 1.3; p = 0.09), but it was not significant. Postpartum iron sucrose injections were significantly less frequent in the TA than the control group (2.2% versus 9.9%; p < 0.05).

Conclusions: A policy of high-dose TA in PPH after vaginal deliveries was not associated with a significant reduction of blood loss.
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http://dx.doi.org/10.3109/14767058.2015.1056731DOI Listing
December 2016

Optimal timing for delivery in case of placenta previa: late-preterm or early-term?

J Matern Fetal Neonatal Med 2016 11;29(9):1498. Epub 2015 Jun 11.

b Department of Obstetrics and Gynecology , Saint Joseph University , Beirut , Lebanon.

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http://dx.doi.org/10.3109/14767058.2015.1051958DOI Listing
June 2016

Maternal outcomes after uterine balloon tamponade for postpartum hemorrhage.

Acta Obstet Gynecol Scand 2015 Apr 1;94(4):399-404. Epub 2015 Mar 1.

Department of Obstetrics and Gynecology, Angers University Hospital, Angers, France.

Objective: To evaluate maternal outcomes following uterine balloon tamponade in the management of postpartum hemorrhage.

Design: Retrospective case-series.

Setting: Two French hospitals, a level 3 university referral center and a level 2 private hospital.

Population: All women who underwent balloon tamponade treatment for primary postpartum hemorrhage.

Methods: Uterine tamponade was used after standard treatment of postpartum hemorrhage had failed. The study population was divided into two groups, successful cases where the bleeding stopped after the balloon tamponade, and failures requiring subsequent surgery or embolization.

Main Outcome Measures: Success rates.

Results: Uterine tamponade was used in 49 women: 30 (61%) after vaginal delivery and 19 (39%) after cesarean section. Uterine atony was the main cause of hemorrhage (86%). The overall success rate was 65%. Of 17 failures, surgery was required in 16 cases, including hysterectomy in 11, and uterine artery embolization in one case. Demographic and obstetric characteristics did not differ significantly between the success and failure groups. No complications were directly attributed to the balloon tamponade in the postpartum period. Two women had a subsequent full-term pregnancy without recurrence of postpartum hemorrhage.

Conclusions: Balloon tamponade is an effective, safe and readily available method for treating primary postpartum hemorrhage and could reduce the need for invasive procedures.
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http://dx.doi.org/10.1111/aogs.12591DOI Listing
April 2015