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The practice of ovarian stimulation for IVF is undergoing a fundamental re-evaluation as recent data begin to successfully challenge the traditional paradigm that ovarian stimulation should be aimed at the retrieval of as many oocytes as possible, in the belief that this will increase pregnancy rates. An opposing view is that live birth rate should not be the only end-point in evaluating the success of IVF treatment and that equal emphasis should be placed on safety and affordability. The International Society for Mild Approaches in Assisted Reproduction (ISMAAR) committee has carried out an up-to-date literature search, with the evidence being graded according to the University of Oxford's Centre for Evidence-Based Medicine. The recommendations were formulated taking into account the quality of evidence on the efficacy, risk and cost of each intervention. ISMAAR recommends adopting a mild approach to ovarian stimulation in all clinical settings as an increasing body of evidence suggests that mild stimulation is as effective as conventional stimulation, while being safer and less expensive. Mild ovarian stimulation could replace conventional stimulation, thus making IVF safer and more accessible worldwide., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: We aimed at developing a method to recover trophoblastic cells from the cervix through a completely non-invasive approach and obtaining a genetic proof of their fetal nature implying that they can be used for non-invasive prenatal diagnosis (NIPD)., Methods: We studied obstetrical samples from 21 pregnant women between 8 and 12 weeks of gestation scheduled for chorionic villus sampling or undergoing elective termination of pregnancy. A cytobrush was used to extract cells from the external parts of the cervix and transferred to 10 ml of preservative solution. Cells were layered on filters with 8 microns pores using the ISET system (Isolation by SizE of Tumor/Trophoblastic cells) and stained. Putative fetal cells were collected by single cell laser-assisted microdissection and identified as fetal or maternal cells by Short Tandem Repeat genotyping. NIPD was blindly performed on 6 mothers at risk of having a fetus with Cystic Fibrosis or Spinal Muscular Atrophy., Results: Trophoblastic cells were recovered from all tested cervical samples with a frequency of 2-12 trophoblasts per 2 ml. NIPD was blindly obtained and verified in 6 mothers at risk of having a fetus with Cystic Fibrosis or Spinal Muscular Atrophy., Discussion: Although larger confirmation studies are required, this is the first report providing a solid proof of principle that trophoblasts can be consistently and safely recovered from cervical samples. Since they are a source of pure fetal DNA, i.e. fetal DNA not mixed with maternal DNA, they constitute an ideal target to develop NIPD of recessive diseases, which is a technical challenge for methods based on cell free DNA., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This study sought to determine whether a reliable non-invasive prenatal diagnosis (NI-PND) of cystic fibrosis (CF) or spinal muscular atrophy (SMA) can be achieved through analysis of circulating fetal trophoblastic cells (CFTC). The kinetics of CFTC circulation were also studied. CFTC were isolated by isolation by size of epithelial tumour/trophoblastic cells at 9-11 weeks of gestation, before chorionic villus sampling (CVS), from the blood of 63 pregnant women at 25% risk for having a child affected by either CF (n=32) or SMA (n=31). Collected cells were laser-microdissected, short tandem repeat-genotyped to determine fetal origin and blindly assessed for mutation analysis. CFTC were independently analysed weekly (4-12 weeks of gestation) in 14 women who achieved pregnancy following IVF. Diagnostic results were compared with those obtained by CVS. All seven CF and seven SMA pregnancies carrying an affected fetus were correctly identified as well as non-affected pregnancies. CFTC provided 100% diagnostic sensitivity (95% CI 76.8-100%) and specificity (95% CI 92.7-100%) in these 63 consecutive pregnancies at risk for CF or SMA. CFTC were found to circulate from 5 weeks of gestation and can be used to develop an early and reliable approach for NI-PND. We sought to determine whether a reliable non-invasive prenatal diagnosis (NI-PND) of two rare genetic diseases - cystic fibrosis (CF) and spinal muscular atrophy (SMA) - can be achieved through analysis of circulating fetal trophoblastic cells (CFTC) in blood of pregnant women. We also studied the time of appearance and circulation of CFTC in maternal blood. CFTC were isolated from maternal blood by isolation by size of epithelial tumour/trophoblastic cells (ISET; an approach for cell isolation from blood) at 9-11 weeks of gestation before chorionic villus sampling (CVS) from the blood of 63 pregnant women at 25% risk for having a child affected by either CF (n=32) or SMA (n=31). Collected cells were analysed by genetic test to determine fetal origin and blindly assessed for mutation analysis. We independently analysed CFTC in maternal blood samples taken weekly (4-12 weeks of gestation) from 14 women who achieved pregnancy following IVF. Diagnostic results were compared with those obtained by CVS. All seven CF and seven SMA pregnancies carrying an affected fetus were correctly identified as well as non-affected pregnancies. CFTC provided 100% diagnostic sensitivity and specificity in these 63 consecutive pregnancies at risk for CF or SMA. CFTC were found to circulate from 5 weeks of gestation and can be used to develop an early and reliable approach for NI-PND., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The recent emergence of oncofertility raises the question of ovarian stimulation and its risks when performed for oocyte or/and embryo cryopreservation in a fertility preservation program. The relation between ovarian stimulation and cancer has been marked by the possible direct or indirect tumorigenic role for pituitary gonadotrophins in the tumorogenesis. Although the growth of many gonadal and extragonadal tumors is stimulated by gonadal sex hormones, whose production is regulated by gonadotrophins, there is still a lack of data to consider FSH and LH as tumor promoters. The purpose of this brief review is to present on one hand, the questions raised by the administration of exogenous gonadotrophins in cancer patients and on the other, to evaluate both experimental and clinical data about the possible relation between gonadotrophins and tumorogenesis., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The French law regulating assisted reproductive technologies forbids donor spermatozoa to be available in case of failed testicular sperm extraction (TESE) performed on the day of oocyte retrieval. This article reports the first French live birth after intracytoplasmic sperm injection of donated spermatozoa into frozen-thawed oocytes cryopreserved following failure of TESE. By reinforcing the relevance of TESE performed on the day of oocyte retrieval, oocyte cryopreservation in couples having beforehand consented to go to sperm donation will avoid cycle cancellation and potentially lead to successful live birth. Therefore, it could modify the French policy of management of patients suffering from non-obstructive azoospermia., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: Ligation of the internal iliac arteries and embolization of the uterine arteries are two techniques routinely used in the management of postpartum hemorrhage. The objective of this study was to examine the long-term consequences of these techniques on women's subsequent reproductive outcome and subsequent delivery morbidity., Methods: Retrospective study including women who underwent ligation and those who underwent embolization, for the treatment of postpartum hemorrhage. We analyzed resumption of menses, fertility, pregnancy and delivery outcome after each treatment., Results: The study included 85 women who underwent ligation and 90 who had embolization to treat postpartum hemorrhage. No adverse event related to menses, fertility, or pregnancy outcome followed either treatment. However, the rate of recurrent hemorrhage was high: 26% after ligation and 39% after embolization. All recurrences were treated medically in the ligation group, but in the embolization group, 42% (five of 12 patients) required invasive treatment and 33% (four patients) transfusions., Conclusion: From the perspective of subsequent menses, fertility and pregnancy outcome, both ligation and embolization are safe procedures for the management of postpartum hemorrhage. However, our results showed a high risk of recurrent postpartum hemorrhage after both treatments. Recurrences seemed more serious after the latter., (Copyright © 2012. Published by Elsevier Masson SAS.)

Introduction: This retrospective study aimed at analyzing IVF-ET management and outcome after cancellation of a first cycle for poor response., Patients and Method: One hundred and forty-two infertile patients were included in this observational study. After an overall analysis on the outcome of the second IVF-ET attempt, a sub-analysis was performed according to the presence or the absence of poor prognostic criteria defined as mentioned: patient age superior to 38 years old, antral follicle count (3-9 mm in diameter) inferior to 10 on cycle day 3 and day 3 serum AMH and FSH levels less than 1 ng/mL and more than 10 IU/mL, respectively. Main outcome measures were the cancellation rates, pregnancy and live birth rates., Results: When a controlled ovarian stimulation was performed, patients with poor prognosis had higher cancellation rates (37.8% vs. 13.3%, P<0.004) and lower pregnancy and live birth rates (22.2% vs. 35.0%, P<0.05 and 11.1% vs. 26.1%, P<0.05, respectively) as compared to good prognosis women., Conclusion: The relatively high cancellation rate in patients with poor prognosis raises the question of the use of IVF modified natural cycle in this group., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Growing evidence indicates that mild ovarian stimulation for in vitro-fertilization-embryo transfer may be an interesting approach to reduce the incidence and severity of complications, the number of treatment days, cost, patient discomfort and number of patient drop-outs. However, the heterogeneity of FSH-sensitive follicles, presumably requires multiple follicular growth to improve oocyte-embryo selection. In addition, whether the acceptability probably is similar between standard ovarian stimulation and mild stimulation, per-treatment pregnancy rates with conventional stimulation is superior to mild stimulation in unselected populations. Hence, some specific indications tend to emerge such as alterations of the ovarian follicular reserve in women of less than 38 years, bad embryo qualities and implantation failure after conventional stimulation, patients with previous history of hyperstimulation syndrome or contraindications to hyperoestrogenia (estrogeno-related cancers and thromboembolic diseases). However, no randomized trials have ever been performed to compare the results of mild versus conventional stimulation in young patients and good responders. Therefore, there is insufficient scientific evidence to shift from standard stimulation to mild stimulation for all patients. Cultural standards have to be considered in the choice of the type of stimulation., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Study Objective: To assess the fertility and obstetric outcome after surgical treatment of complete uterine and vaginal septum., Design: Retrospective study (Canadian Task Force Classification II-2)., Setting: Teaching hospital in France., Patients: Twenty-two women who have experienced infertility, pregnancy losses, dyspareunia, or dysmenorrhea., Intervention: Hysteroscopic section of complete uterine septum and resection of longitudinal vaginal septum., Measurements and Main Results: Improvement of dyspareunia or dysmenorrhea and obstetric outcome, focusing on the miscarriage rate, obstetric complications, and the gestational age at delivery were assessed. Overall, 20 women had conceived a total of 37 pregnancies, with 10 and 8 deliveries before and after metroplasty, respectively. Median gestational age at delivery was not significantly different in both groups (36.5 [33-39.5] vs 38.0 weeks' gestation [35-40], respectively). Preterm delivery occurred in 4 cases (25%) before the surgery and in 3 cases (14%) after (p = .44). The live birth rate was also not significantly different before and after surgery (62.5% and 38%, respectively) (p = .19). There was a decrease of caesarean section and significantly fewer breech deliveries after metroplasty (p = .01). A decrease in the prevalence of dyspareunia or dysmenorrhea was observed after metroplasty in the 19 patients originally displaying these symptoms. No perioperative complications were observed in this series., Conclusion: Resection of vaginal septum and hysteroscopic metroplasty for complete uterine septum with resection of the cervical septum is a safe procedure that may improve dyspareunia and dysmenorrhea when present. Reproductive and obstetric outcomes after this procedure do not appear to be compromised, even though a relatively high miscarriage rate remains after metroplasty, questioning its systematic practice in symptom-free women without any previous obstetric history., (Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.)

Study Objective: To estimate the accuracy of 3-dimensional (3-D) ultrasonography in the differential diagnosis of septate and bicornuate uterus compared with office hysteroscopy and pelvic magnetic resonance imaging (MRI)., Design: Prospective cohort study (Canadian Task Force Classification II-2)., Setting: University hospital., Patients: Thirty-one patients referred with a suspected diagnosis of septate (n = 20) or bicornuate (n = 11) uterus., Interventions: All patients underwent 3-D ultrasonography displaying the rebuilt coronal view of the uterus, office hysteroscopy, and pelvic MRI. Operative hysteroscopic assessment and treatment was performed in case of sonographically diagnosed septate uterus. Bicornuate uterus was confirmed by laparoscopy., Main Outcomes Measures: Concordance between suspected diagnosis with 3-D ultrasonography, hysteroscopy, and pelvic MRI and final diagnosis., Results: A septate uterus was diagnosed with 3-D ultrasonography in 29 patients and bicornuate uterus in 2 patients. Hysteroscopic transcervical section of the uterine septum was achieved in the 29 patients. Bicornuate uterus was laparoscopically confirmed in the 2 patients. Concordance between ultrasonography and operative hysteroscopy or laparoscopy was verified in all 31 cases. Twenty-five uterine septa and 5 bicornuate uteri were diagnosed by hysteroscopy (3 false-positive diagnoses of bicornuate uterus, 1 unfeasible hysteroscopy). Hysteroscopic diagnosis was correct in 27/30 patients. Twenty-four septate uteri and 7 bicornuate uteri were diagnosed by MRI (5 false-positive diagnoses of bicornuate uterus). Two complete septate uteri diagnosed by MRI were finally confirmed as incomplete septate uteri after 3-D ultrasonography and operative hysteroscopy. MRI diagnosis was correct in 24/31 patients., Conclusion: Transvaginal 3-D ultrasonography appears to be extremely accurate for the diagnosis and classification of congenital uterine anomalies, more than office hysteroscopy and MRI. It may conveniently become the only mandatory step in the assessment of the uterine cavity in patients with a suspected septate or bicornuate uterus., (Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.)

Preimplantation genetic diagnosis (PGD) is authorized in France since 1999. After 10 years, technical results are encouraging. With the development of new technologies, our team is able to diagnosis the large majority of chromosome translocations and 75 monogenic diseases. However, PGD remains limited because of the growing augmentation of demands causing an increasing delay for the first procedure of more than 18 months. Since 2006, 19 couples asked for a PGD with HLA typing. In January 2011, 11 couples have already been included in our PGD program. The birth of the first child after PGD with HLA typing offers new perspectives of treatment for these couples., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The ovarian hyperstimulation syndrome is a major complication of ovulation induction for in vitro fertilization, with severe morbidity and possible mortality. Whereas its pathophysiology remains ill-established, the VEGF may play a key role as well as coagulation disturbances. Risk factors for severe OHSS may be related to patients characteristics or to the management of the ovarian stimulation. Two types of OHSS are usually distinguished: the early OHSS, immediately following the ovulation triggering and a later and more severe one, occurring in case of pregnancy. As no etiologic treatment is available, the therapeutic management of OHSS should focus on its related-complications. Thrombotic complications that can occur in venous or arterial vessels represent the major risk of OHSS, possibly conducting to myocardial infarction and cerebrovascular accidents. Once the OHSS is diagnosed, prevention of thrombotic accidents remains the major issue., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Over the past two decades, major advances in diagnostic modalities and treatment have markedly improved rates of cure for adult cancers. As a consequence, the number of long-term survivors is increasing, and fertility preservation has become a major issue for young patient about to start treatment for cancer. Whether fertility preservation is a promising option, most of the technologies currently used are far from being well established or are even still experimental. Patients should be aware that no method guarantees success. Psychological and ethical impacts of fertility preservation are major concerns and should be included in the multidisciplinary approach of the patients., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

A 34-year-old woman consulted the day before a scheduled caesarean for dry cough. A positive rhinopharyngeal sample for PCR testing for influenza A H1N1 led to a curative oseltamivir (Tamiflu®) treatment. At delivery a direct contact between the newborn and mother lasted only few seconds. The first healthy baby boy developped dry cough with a rhinopharyngeal sample positive for A H1N1. The minimal contact between mother and child and the positive neonatal sample only four hours after birth allow to think that it is a rare case of prenatal transmission of influenza A H1N1 to the fetus., (Copyright © 2011. Published by Elsevier Masson SAS.)

To reduce the twin pregnancy rate and their morbidity, several recommendations have been proposed to practice the "elective single embryo transfer" in a selected population. We decided to apply the criteria that were proposed in five articles from the literature to our population to evaluate the percentage of our population concerned and the impact on our twin pregnancy rate. The result is that these criteria only concern 2,4 to 10,8% of our population with a minor reduction of our twin pregnancy rate with a potential lake of chance concerning the pregnancy rate. We should study others possibilities than the population's criteria to reduce the number of embryo transferred., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Behçet's disease is a multisystemic disease of unknown origin characterized by a recurrent bipolar aphtosis (oral and genital) associated with vascular, digestive or articular symptoms. Gynecologists can be faced to this disease at any time of the life of their patients, including during the pregnancy. Given that the first demonstrations of the disease can be genital, they are in the front line to evoke this diagnosis. They thus have to know the main characteristics of the disease to make the diagnosis and to organize a multidisciplinary management. During pregnancy, the treatment of the disease is to be adapted to avoid teratogenic drugs, and adapt the doses of the treatment., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

The objective is to compare the IVF procedures in modified natural cycle outcomes according to serum anti-Mullerian hormone (AMH) levels. We included in this retrospective study 342 patients undergoing their first IVF in modified natural cycle. Patients were regrouped in three groups according to their serum AMH level: group 1 was defined by patients with AMH level<0.97 ng/mL (<25th percentile), group 2, patients with AMH level between 0.97 ng/mL and 2.60 ng/mL (25-75th percentile), and group 3, patients with AMH level between 2.61 ng/mL and 6.99 ng/mL (>75th percentile). The main outcomes were cancellation rate, embryo transfer rate and clinical pregnancy rate, ongoing pregnancy rate and implantation rate. No difference has been observed on cancellation rate, embryo transfer rate, clinical pregnancy rate and implantation rate. The ongoing pregnancy rate per IVF cycle was respectively: 12.8±3.6% for AMH inferior to 0.97 ng/mL versus 12.5±2.5% for AMH between 0.97 to 2.60 ng/mL and 13.4±4.2% for AMH between 2.61 ng/mL and 6.99 ng/mL. In conclusion, IVF in modified natural cycles procedures should be considered as an option for patients with an altered ovarian reserve defined by a serum AMH inferior to 1 ng/mL. Serum AMH level seems a quantitative marker of the ovary but not a quality factor. Serum AMH level does not seem to be a prognostic factor for ongoing pregnancy rated in IVF modified cycles., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Intra-uterine growth retardation (IUGR) is a frequent cause of consultation in antenatal care unit. The prognosis relies on the etiology: vascular, chromosomic, genetic, or infectious. Because of chronic fetal distress, hypotrophy increase morbidity, mortality and neurosensorial long term effect. Usually, infection is involved in 5 to 15% of the IUGR, mainly by Cytomegalovirus (CMV), Varicella Zoster virus, rubella, toxoplasmosis, herpes and syphilis. Maternal sera and amniotic liquid analysis make the diagnosis possible but fetal ultrasound scan is used to find other features. Most of the abnormalities are unspecific but their combination can worsen fetal prognosis. Infection should always be ruled out in the assessment of IUGR., (Copyright © 2011. Published by Elsevier Masson SAS.)

Although female cancer incidence may be on rise, antineoplastic regimens have become more successful. As a result, an increasing number of women with cancer survive to endure the long-term consequences of chemotherapy. One of the most important long-term consequences of cancers treatments in young female is premature ovarian failure and infertility. Because of the increasing survival rates, many of these young women are seeking methods to preserve their fertility. Currently, embryo/oocytes cryoporeservation obtained after ovarian stimulation appears to provide the best fertility preservation option. However, patients may not have sufficient time to undergo ovarian stimulation prior to chemotherapy and/or the hormones used in ovarian stimulation are contra-indicated for estrogen-dependant tumors. In vitro maturation of oocytes (IVM) has been suggested to avoid ovarian stimulation and time requirement in patients with cancer, and can be combined with ovarian tissue cryobanking. In this review, we will discuss the position of IVM in the strategy of fertility preservation in young women., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objective: Analyzing the results and validating the procedure of testicular sperm extraction (TESE) performed on the day of oocyte retrieval in non obstructive azoospermia (NOA) patients., Patients and Methods: Sixty TESE were performed on the day of oocyte retrieval (dOR), in 52 NOA men. Patients were sorted into three groups according to the results of the surgical procedure: 1: sperm recovery with possible sperm freezing (n=20); 2: sperm recovery without freezing (n=27); 3: "negative" biopsy (n=13). ICSI outcomes in the two groups with sperm recovery were compared to those of ICSI performed with frozen-thawed sperm obtained from TESE performed (n=13)., Results: The rate of positive sperm retrieval was 78%. While the overall clinical pregnancy rate was 50%, no difference in the fertilization, implantation and clinical pregnancy rates was found in the two groups with positive sperm retrieval as compared to frozen-thawed sperm group. Twelve pregnancies were obtained in patients without further sperm cryopreservation., Conclusion: After TESE in NOA men, cryopreserved sperm produced comparable results with freshly obtained sperm. However, TESE performed on dOR can offer the opportunity, in patients with rare sperm that might not survive freeze-thaw, to have a possible fresh embryo transfer. Couples should be counselled regarding the possibility of oocyte retrieval without sperm for ICSI., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Purpose of Review: The purpose of this review is to update the reader on the impact of cancer treatment on fertility, the options of fertility preservation, and the new markers to assess ovarian function., Essential Points: The impact of chemotherapy and radiotherapy on fertility depends on the drugs and the doses used. It often affects ovarian reserve significantly, and the presence of menstruation is not a reliable reflection of it. Fertility preservation techniques, such as ovarian protection, and preferably cryopreservation combined with assisted reproductive medicine, should be individually discussed and possibly proposed to the patients. The use of new markers for ovarian reserve assessment will help to evaluate infraclinic chemotherapy and/or radiotherapy-induced effects on ovarian reserve, prior to clinical effects., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

All indicates that anti-Müllerian hormone (AMH), though initially studied for its importance on male development, plays an inhibiting role on the initial and cyclic processes of follicular recruitment. The aspects involved in its regulation are still poorly understood, but the oocyte, some steroids, and follicular development itself seem to be involved. In addition, AMH has become an important clinical marker of ovarian functioning for many reasons, including its exclusive production by granulosa follicles at many stages of development, its probable FSH independence, its low inter and intracycle variability and its reliable quantitative (qualitative?) relationship with ovarian follicles and their response to exogenous FSH. The growing interest in ovarian AMH incited us to review some important fundamental and clinical publications in this field., (Copyright 2010. Published by Elsevier SAS.)

Growing evidence indicates that androgens play a positive role in follicle proliferation and growth. Hence, many authors have assumed that androgen supplementation in women with poor ovarian reserve might improve the number of antral follicles available for ovarian stimulation. As androgen administration may become more frequently used in reproductive medicine, this study aimed at describing the histological changes observed in the genital tract and the breast of female-to-male (FTM) transsexuals. A pathological analysis of the genital tract of 112 FTM subjects who were given androgen for at least 6 months before hystero-salpingo-oophorectomy was performed. In addition, 100 bilateral mastectomies were performed, allowing a study of the breast tissue. Mean ovarian volume was increased, with histological characteristics of polycystic ovaries (PCO), defined as >12 antral follicles per ovary, observed in 89 patients (79.5%). Endometrial atrophy was observed in 45%. Breast examination revealed marked reduction of glandular tissue and increase of fibrous connective tissue in 93%, without atypical hyperplasia or carcinoma. The present data confirms and expands the putative associations between long-term androgen administration and abnormalities in ovarian architecture with macroscopic and microscopic characteristics of PCO, increased risk of endometrial atrophy and fibrotic breast tissue with marked glandular reduction., (Copyright (c) 2009 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Pandemic influenza A H1N1 2009 is a benign disease when infecting healthy adults, but it can lead to severe consequences in pregnant woman, for the fetus or its mother. The incidence of the disease is increasing strongly, and health authorities estimate that one third of the world population might be infected before the end of the winter. Diagnosis of infection with influenza virus H1N1 is suspected when a patient presents with the association of symptoms of the respiratory tract like sore throat, cough, or dyspnea, with general signs like fever, myalgias, or exhaustion. Diagnosis confirmation is obtained with nasopharyngeal swab and virus detection with molecular biology. This flu can lead to severe consequences for the pregnant woman and fetus. For this reason, it is advisable to treat pregnant women systematically by oseltamivir or zanamivir, and to treat preventively the pregnant woman in case of close contact with a suspected or confirmed infected person. Even if the management of influenza A H1N1 2009 infection during pregnancy relies on family physicians and gynecologists, every physician having in charge such cases should regularly update his knowledge regarding the evolution of the recommendations for the pandemic.

We report on the feasibility, efficiency, and reproductive outcomes of hysteroscopic resection of late residual trophoblastic tissue in 50 patients in an observational study over 6 years. Complete evacuation of the uterus was achieved in all patients by hysteroscopy. The median operative time was 21 (15-30) min. Only one surgical complication was registered: a uterine perforation in a patient with previous metroplasty. Hysteroscopic resection of persistent trophoblastic tissue seems to be a safe and efficient procedure that could be proposed as an alternative to conventional non-selective blind curettage. We would also recommend systematic second-look hysteroscopy to asess the exact prevalence of post-procedure intrauterine adhesions.

The prenatal diagnosis of abdominal mass poses the problem of its origin. Renal tumors are rarer than neuroblastoma but they are most often congenital mesoblastic nephroma. The congenital mesoblastic nephroma has a good forecast in spite of a sonographic impressive aspect. MRI can help to locate tumor but cannot tell difference between the different kinds of renal tumor. Prenatal forecast is especially linked with hydramnios and hydrops fetalis. Histolological study of the tumor is important for the prognosis. Two morphological subtypes are currently distinguished: the classic type with a good forecast and the atypical or cellular type. Distant metastases have been related only to the cellular form but especially in infants aged more than 3 months and never in the newborns. The diagnosis of the tumor does not change the mode of delivery except in case of an important volume. Complications are searched during the first days of life: hypertension, hypercalcemia, vomiting, hyperreninemia. Radical nephrectomy is performed after the end of the first week. In case of a classic form, the healing is always obtained. In case of cellular form, distant metastases are searched. In any rate, the follow-up is recommended until the end of the growth.

Objectives: To evaluate quality control impact, in assisted reproductive medecine, in view of the stability of results., Materials and Methods: Prospective collection of all IVF cycles at the center of AMP at Antoine-Béclère hospital (Clamart), as well as pregnancy outcomes, from 2002 till 2006., Results: 44.3% in the clinical pregnancy rate and 38.0% in the delivery rate per oocyte retrieval. These rates are stable during the five years studied. The rate of multiple pregnancy is of 30.7%, decreasing, with the decrease in number of transferred embryos., Conclusion: Results are stable over five years duration. Quality control seems to be necessary.

The accurate assessment of ovarian reserve is an essential step before the treatment of infertile couples. Ovarian reserve could either be evaluated through clinical or biological parameters, but ultrasound plays a remarkable role, since it permits the direct visualization and count of ovarian antral follicles. Nevertheless, the available literature data are conflicting about the real sensibility and specificity of this method to predict the exact number of retrieved oocytes or the occurrence of pregnancy after a procedure for medical assisted reproduction. New technologies have been developed, as the 3D-ultrasound, who does not ameliorate ultrasound accuracy, but permits the reduction of the time necessary for patient's examination and virtually eliminates inter- and intra-observer bias. The place of the ovarian artery flow evaluation by Doppler remains unclear and need more studies.

We have isolated c-Kit(+)Lin(-) cells from both human and murine amniotic fluid (AF) and investigated their hematopoietic potential. In vitro, the c-Kit(+)Lin(-) population in both species displayed a multilineage hematopoietic potential, as demonstrated by the generation of erythroid, myeloid, and lymphoid cells. In vivo, cells belonging to all 3 hematopoietic lineages were found after primary and secondary transplantation of murine c-Kit(+)Lin(-) cells into immunocompromised hosts, thus demonstrating the ability of these cells to self-renew. Gene expression analysis of c-Kit(+) cells isolated from murine AF confirmed these results. The presence of cells with similar characteristics in the surrounding amnion indicates the possible origin of AF c-Kit(+)Lin(-) cells. This is the first report showing that cells isolated from the AF do have hematopoietic potential; our results support the idea that AF may be a new source of stem cells for therapeutic applications.

Novel embryonic stem cell lines derived from embryos carrying structural chromosomal abnormalities obtained after preimplantation genetic diagnosis (PGD) are of interest to study in terms of the influence of abnormalities on further development. A total of 22 unbalanced blastocysts obtained after PGD were analysed for structural chromosomal defects. Morphological description and chromosomal status of these blastocysts was established and they were used to derive human embryonic stem cell (ESC) lines. An outgrowth of cells was observed for six blastocysts (6/22; 27%). For two blastocysts, the exact morphology was unknown since they were at early stage, and for four blastocysts, the inner cell mass was clearly visible. Fifteen blastocysts carried an unbalanced chromosomal defect linked to a reciprocal translocation, resulting in a positive outgrowth of cells for five blastocysts. One human ESC line was obtained from a blastocyst carrying a partial chromosome-21 monosomy and a partial chromosome-1 trisomy. Six blastocysts carried an unbalanced chromosomal defect linked to a Robertsonian translocation, and one showed a positive outgrowth of cells. One blastocyst carried an unbalanced chromosomal defect linked to an insertion and no outgrowth was observed. The efficiency of deriving human ESC lines with constitutional chromosomal disorders was low and probably depends on the initial morphological aspect of the blastocysts and/or the type of the chromosomal disorders.

BCL2-associated X protein (BAX) and B-cell leukaemia/lymphoma gene-2 (BCL2), which are, respectively, pro- and anti-apoptotic proteins of the BCL2 gene family, participate in the mitochondria-dependent apoptosis pathway. A correlation between low incidence of apoptosis in cumulus cells and oocyte maturation has previously been suggested in ovarian stimulation. However, little is known in unprimed ovaries. These authors have investigated whether BAX and BCL2 expression in cumulus cells affects the competency of in-vitro matured oocytes. We have studied 100 cumulus-oocyte-complexes (COC) recovered from unprimed ovaries of 13 women diagnosed with polycystic ovary syndrome (PCOS) and undergoing in-vitro maturation (IVM) with their informed consent. COC were matured for 24 h in a specific maturation medium and the cumulus was stripped from the oocyte. BAX and BCL2 mRNA content was measured in each COC using real-time polymerase chain reaction. We found that BCL2 mRNA expression was significantly higher in cumulus cells associated with mature oocytes than those associated with immature oocytes while BAX mRNA concentrations did not vary in cumulus cells. Regarding fertilization, higher BCL2 mRNA content was found in cumulus cells enclosing fertilized oocytes (0.140 versus 0.075; P = 0.03). These results suggest that BCL2 expression is strongly associated with the ability of oocytes to complete nuclear maturation and to be fertilized.

Cervical cerclage is a common surgical technique that has been used for more than 50 years to prevent preterm deliveries and in the management of a threatened second trimester loss. However, it remains one of the most controversial interventions in obstetrics and this is probably due to difficulties in diagnosing cervical insufficiency, which is based on a history of recurrent second trimester loss or early preterm delivery following painless cervical dilatation in the absence of contractions or bleeding. This article reviews in 2008 the current literature regarding the efficacy of elective cerclage, ultrasound-indicated cerclage, emergency cerclage, and cervico-isthmic cerclage for singletons and multiple pregnancies.

Two major functions are assumed by the testis: the production of male gametes (that is, spermatozoa) and the production of steroid hormones. Both two functions are established during fetal life and are essential to the adult fertility and the masculinization of the internal tract and genitalia. For many years, our laboratory has been interested in the ontogeny of those two functions in rodents and, since 2003, in collaboration with gynecology and obstetrics service of professor R. Frydman in Antoine-Béclère hospital, we have studied them in human. The first aim of this work was to improve the global knowledge of the human fetal testis development by using both our experimental data and the literature. Then, we focused on the different defects that can occur during the fetal testis development. Indeed, male reproductive abnormalities have been steadily increasing since the last decades and are thought to be related to the concomitant increase of the concentration of contaminants and particularly of endocrine disruptors in the environment. Thus, we decided to study the effect of endocrine disruptors on human fetal testis and, more particularly, the effect of phthalates, by using an organ culture system developed for human. In contrast to the data obtained in rat, mono (ethylhexyl)-phthalate (MEHP), an active metabolite of the most widespread phthalate in the environment, does not disturb the steroidogenic function. On the other hand, it has a negative effect on the male germ cells number. This study is the first experimental demonstration of a negative effect of phthalates directly on human fetal testis.

Objective: The aim of this study was to assess hourly fetal urine production rates (HFUPRs) and establish a nomogram by measuring bladder volumes with 3-dimensional ultrasound., Study Design: Fetal urine bladder volume was estimated in 167 normal singleton pregnancies with neither oligohydramnios nor polyhydramnios, at a gestational age of 20-41 weeks. HFUPR was estimated in a regression analysis that included at least 3 volumes calculated during the filling phase with the Virtual Organ Computed-aided AnaLysis (VOCAL) technique. We estimated interoperator variability for HFUPR less than 10 mL/h and HFUPR greater than 10 mL/h., Results: Fetal urine production rates at 25, 30, 35, and 40 weeks were 7.5, 22.2, 56.1, and 125.1 mL/h, respectively. The intraclass correlation coefficients for interoperator variability were 99.2% for HFUPR less than 10 mL/hour and 97.1% for HFUPR greater than 10 mL/h., Conclusion: Prenatal measurement of HFUPR with 3-dimensional VOCAL ultrasound is reproducible and may help to determine the cause and prognosis of amniotic fluid volume abnormalities.

Objectives: The aim of this study is to determine the complications of third trimester amniocentesis for fetal karyotyping among women unwilling to accept the fetal loss risks of second trimester amniocentesis., Materials and Methods: A retrospective study was carried out from January 1998 to December 2006 of 182 singleton pregnancies that underwent a late amniocentesis (after 32 weeks) for fetal karyotyping. The indications were integrated risk (maternal age, first trimester nuchal translucency, second trimester maternal serum markers) over 1/250 (n=68), isolated maternal age over 38 years (n=51), isolated abnormal second trimester biochemical markers (n=34), history of personal or familial a chromosomal abnormality (n=21) or maternal choice (n=8). Presence of fetal abnormalities at ultrasound or context of viral or parasitologic seroconversion as well as multiple pregnancies were considered as non-inclusion criteria., Results: Median maternal age and gestational age at sampling were 39 years (range 23-48) and 32.4 weeks (29.5-37.6). Median interval between amniocentesis and definitive results of amniocentesis on the one hand, and delivery on the on the hand were 15 days (7-42) and 47 days (8-69), respectively. There were no chromosomal abnormality and non-termination of pregnancy. Nine patients out of 182(5%) had a spontaneous labour followed by premature delivery before 37 weeks and six women (3.3%) among those nine displayed preterm premature rupture of membranes (PPROM). Four patients out of 182 (2%) gave birth before definitive karyotyping result but all of them had a direct fluorescence in situ hybridisation analysis with a normal karyotyping result known well before delivery., Conclusions: The risk of preterm premature rupture of membrane is 3.3%, with a 5% risk of premature delivery before 37 weeks. This late procedure provides a safe reassurance to women who are unwilling to accept the risks of earlier amniocentesis. However, it should only be used in particular situation and in countries were legislation allows late termination of pregnancy.

We present a rare case of prenatal diagnosis of two de novo chromosome structural rearrangements including a translocation (1;3) associated with a 22q11.2 deletion. The amniocentesis was performed because the systematic ultrasound examination revealed: right aortic cross with double aortic arch, with normal size of aorta and pulmonary artery. Our report emphasises that 22q11.2 deletion must be looked for when a fetal cardiac conotruncal malformation is diagnosed, even in the presence of another chromosomal abnormality. In prenatal diagnosis, this can have implication for patient management and genetic counselling.

Aim: The aim of this study was to report our experience concerning a role-playing approach for the teaching of physician-patient relationship., Methods: The role-playing two-day course was designed to be highly interactive for a small group (ten participants). Opinions were gathered by an anonymous structured questionnaire (ten questions) completed by the participants and focused on their view of the play role and the physician-patient relationship., Results: The opinions of the participants were highly positive; all appreciated the courses. The strong emotional involvement was considered beneficial for all of them, sharing emotional aspects of the profession, and usefulness in clarifying opinions on the physician-patient relationship., Conclusion: The positive opinions recorded during this experience suggest the benefit of implementing non-conventional educational approaches, such as role-play, to highlight the relative importance of physician-patient relationship in obstetrics and gynecology.

Objectives: To assess amniocentesis practice of a network during one year., Materials and Methods: In a retrospective multicenter study of the south-west Francilian network, we have enrolled 2400 patients who underwent amniocentesis, from 1 January 2003 to 31 December 2003., Results: The rate of amniocentesis was 9.5%. The most frequent indication was a positive maternal serum screening test result (44%). The rate of global fetal losses (spontaneous miscarriage and intrauterine death) was 1.4%. Once the fetuses with aneuploidy and lethal pathology excluded, the rate of global fetal losses potentially related to amniocentesis was 1.21%. The rate of premature rupture of the membranes was 1.12% and prematurity affected 6.5% of the living births., Conclusion: Our study has highlighted several practices of amniocentesis within the network. Overall, amniocentesis potentially induces 1.12% of fetal losses. Screening tests are currently used sequentially, which leads to an increase number of amniocentesis and to an increase number of losses of "a priori" healthy fetus. Only the use of a combined screening could lower the frequency of amniocentesis without decreasing the detection rate of chromosome abnormalities.

In-vitro maturation of oocytes (IVM) is a new IVF technology developed in order to avoid iatrogenic complications of standard IVF treatments. This technique is particularly useful in patients suffering from polycystic ovary syndrome (PCOS) who are concerned with the risk of ovarian hyperstimulation syndrome. This technique is nowadays routinely practised in many international centres. However, the efficiency of this technique needs to be improved for a better support of maturation conditions to maximize oocyte developmental competence. In order to improve IVM results, the efficiency of two IVM media was retrospectively compared. Ninety-three PCOS candidates undergoing their first IVM cycle were included in this study, and IVM was conducted with TCM-199 or IVM-Medicult medium. This is the first study comparing two maturation media. Both media resulted in the same results concerning total oocyte maturation, fertilization, early embryo development and pregnancy rates.

The objective of this study was to assess the reproductive competence of oocytes obtained by follicular flushing in poor responder patients. This prospective comparative study, at the University of Paris XI, Assistance Publique des Hopitaux de Paris, INSERM Unit 782, was performed on 165 infertile IVF embryo transfer candidates. A total of 271 consecutive minimal stimulation IVF cycles were studied. Oocyte retrieval was performed 34 h after human chorionic gonadotrophin administration and oocytes were allocated into two groups according to their retrieval method: oocytes obtained in the first follicular aspiration (FA, n = 127); and oocytes retrieved in the subsequent follicular flushing (FF, n = 102). The principal outcome was to evaluate clinical pregnancy and embryo implantation rates. Thus, patient characteristics, fertilization rate and clinical pregnancy rate per oocyte were comparable in both of groups. In contrast, embryo morphology (41 versus 59%, P < 0.01) and implantation rates (20.4 versus 34.8%, P < 0.04) were better in the FF group. In conclusion, an optimal reproductive competence was observed in oocytes retrieved by follicular flushing in minimal stimulation IVF in poor responder patients.

Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common hereditary renal cystic diseases, and is caused by mutations in the PKHD1 gene. Due to the poor prognosis, there is a strong demand for prenatal diagnosis. Preimplantation genetic diagnosis (PGD) represents an alternative because it avoids the physical and emotional trauma of a pregnancy termination in the case of an affected fetus. A standardized single-cell diagnostic procedure was developed, based on haplotype analysis, enabling PGD to be offered to couples at risk of transmitting ARPKD. Six linked markers within (D6S1714 and D6S243), or in close proximity to (D6S272, D6S436, KIAA0057, D6S1662) the PKHD1 gene were tested by multiplex nested-polymerase chain reaction (PCR), using a Qiagen multiplex PCR kit. PCR analyses were carried out on 50 single lymphocytes. The amplification rate was excellent (100%), with an allele drop-out (ADO) rate ranging from 0 to 8%. Five PGD cycles were performed and 23 embryos were biopsied and analysed using this test. Transferable embryos were obtained in 4 cycles, resulting in two pregnancies and the birth of a healthy boy. This standardized diagnostic procedure allowed the detection of recombination, contamination, and ADO events, providing high assay accuracy with wide applicability.

Introduction: Ovarian cancer is the leading cause of death from gynaecological malignancy, especially because of late diagnosis. The objective of the study was to provide the clinician with current concepts regarding prevention of ovarian cancer., Material and Methods: A computerized search of articles published was performed using the Medline database We performed a review of the literature (PubMed, Embase) using the following search terms (MeSH and non-MeSH): prevention, chemoprevention, chemoprevention, ovarian cancer, ovarian, ovary, carcinoma, tumor, tumour., Results: Oral contraceptive and acetaminophen use may provide substantial protection against ovarian cancer, whereas aspirin, carotenoids and non-steroidal anti-inflammatory agents do not decrease the risk. However, to date, there is no recommendation concerning low risk population. At the opposite, young women (<35-40 years old) presenting with BRCA1 or 2 mutation or Lynch syndrome may be counseled for chemoprevention using oral contraceptive. For high risk women over 35-40 years old, prophylactic bilateral salpingo-oophorectomy should be performed. Indeed, it has been showed that prophylactic surgery significantly decrease mortality rates in high risk women., Conclusion: Large randomized studies are required to assess the efficacy of ovarian cancer chemoprevention in low risk women. High-risk women over 35-40 years old should be counseled for prophylactic salpingo-oophorectomy or for chemoprevention using oral contraceptive.

Objectives: To know the psychological motivations of couples who keep their embryos so long (five years and more) and do not make a decision about them., Patients and Methods: We studied 84 couples refrained from making a decision on their cryopreserved embryos for at least five years. They were invited to fill out a questionnaire focusing on three points: the reasons of the indecision, their own representation of the cryopreserved embryos and their choice for the future: donation to another couple, to research, pregnancy or no solution for the moment., Results: Mean (S.D.) women's and men's age were respectively, 38.8 (2.5)- and 41.3 (2.5)-years old. On average, three (1-9) embryos are preserved since 7.5 (5-12) years. Most of couples are parents. Four major reasons explain their attitudes: feeling of being too aged (25%), fear of a multiple pregnancy (45%), disagreement between members of couple (20%) and fear of failure (42.5%). Multiple choices were given to the future of the embryos: 25% wanted a pregnancy, 8% wanted to give them to infertile couples, 20% to research and 27.5% did not find any solution. Twenty percent were hesitating. The representation of those embryos is more symbolic than material. Most of the time, they see them like a potential child, a hope for the future or a brother or sister of their alive children., Discussion and Conclusion: Those embryos are symbolized. They are a proof of fertility, a hope for another child. So, whatever the legal statement, couples will be in a dilemma because it is never easy for an infertile person to renounce to embryos, and the hope for children.