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International audience; Objective: To provide a snapshot of the surgical management of endometriosis in French high-volume activity centers.Methods: Analysis of prospectively collected data between November 2015 and May 2017 in 21 centers with a high volume of endometriosis surgery in France. Each facility could include up to 40 patients undergoing laparoscopy for endometriosis. Data were collected before and two months after surgery.Results: 361 patients were enrolled in the study. Twenty-seven patients (7.48%) were lost to follow-up at the month 2 visit. Endometriosis stage was I-II in 33.70% of patients and III-IV in 66.30%. Uterosacral ligament resection was the most frequently performed procedure (50.97%) followed by rectal surgery (31.58%), ovarian procedures for endometrioma, procedures for ureters (21.33%) and the bladder (11.91%). Antiadhesion agents were employed in 215/361 (59.56%) patients. The median length of hospital stay after surgery was 2 (IQR 1 − 4) days. Post-operative complications were recorded in 9.34% of patients. Rectovaginal fistulae occurred in 8 patients (2.41%), pelvic abscess in 4 (1.20%) and bladder atony in 3 (0.90%). 17 patients (5.14%) required a second surgical procedure after a median time of 31 days (IQR 9 − 81). Two months after surgery, 95.09% of patients reported being satisfied or very satisfied with the surgery.Conclusion: Our study shows that surgical management of endometriosis in centers with a high volume of endometriosis surgery, mainly concerns women presenting with severe disease and deep localizations, with an overall risk of major complications inferior to 10% and a high rate of patient satisfaction.

Cigarette smoking is associated with lower fecundity rate, adverse reproductive outcomes and higher risk of IVF failure. Over the last decades, prevalence of smoking among women of reproductive age has increased. The aim of this work was first to focus on the knowledge of the effects of cigarette smoking on reproductive stages and particularly on implantation process and early placentation. Human clinical and experimental studies were analysed in order to find hypothesis and explanations for the effects observed. Then, our second aim was to analyse which factors could influence smoke effects. We observed that smoke compounds induce impairment of endometrial maturation, disturb angiogenesis and trophoblastic invasion. Cigarette compounds also impair uterine and endometrial vascularisation and myometrial relaxation. These effects lead to implantation failure in IVF and higher risk of miscarriage. Many factors influence the effects of cigarette smoke, as smoke behaviour, dose and duration of exposition. Sidestream is also damaging on reproductive function. Prenatal exposure leads to irreversible and deleterious effects on ovarian reserve. These observations need to be confirmed in order to improve health care in women of reproductive age.

BACKGROUND Cigarette smoking is associated with lower fecundity rates, adverse reproductive outcomes and a higher risk of IVF failures. Over the last few decades, prevalence of smoking among women of reproductive age has increased. This review focuses on current knowledge of the potential effects of smoke toxicants on all reproductive stages and the consequences of smoke exposure on reproductive functions. METHODS We conducted a systematic review of the scientific literature on the impact of cigarette smoking and smoke constituents on the different stages of reproductive function, including epidemiological, clinical and experimental studies. We attempted to create hypotheses and find explanations for the deleterious effects of cigarette smoke observed in experimental studies. RESULTS Cigarette smoke contains several thousand components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with diverse effects. Each stage of reproductive function, folliculogenesis, steroidogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette smoke components. The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status. Individual sensitivity, dose, time and type of exposure also play a role in the impact of smoke constituents on human fertility. CONCLUSIONS All stages of reproductive functions are targets of cigarette smoke toxicants. Further studies are necessary to better understand the deleterious effects of cigarette smoke compounds on the reproductive system in order to improve health care, help to reduce cigarette smoking and provide a better knowledge of the molecular mechanisms involved in reproductive toxicology.

This study aimed at evaluating parameters and results of ovarian stimulation for myotonic dystrophy type 1 (DM1) female patients undergoing preimplantation genetic diagnosis (PGD) and to assess an eventual association between genotype and ovarian reserve. A retrospective study involved all 17 DM1 patients treated in the study centre's PGD programme. The control group consisted of 22 patients treated for X-linked disorders in the same period. Comparative analysis of ovarian stimulation parameters and results was performed with bivariate and multivariate analysis. Then, among DM1 patients, a correlation between genotype (number of CTG repeats) and ovarian reserve, assessed by antral follicle count, was investigated. Comparative study showed no difference concerning the number of oocytes, embryos and pregnancy rate between the two groups. Multivariate analysis demonstrated that DM1 patients needed a significantly higher dose of gonadotrophins (+544IU, P0.001) than X-linked disorders patients and suggests a decreased ovarian sensitivity. However, with higher dose of gonadotrophins, PGD for DM1 offers good reproductive outcomes with a clinical pregnancy rate of 35.7%. Genotype was not correlated to ovarian reserve and appeared not to be helpful for the choice of the dose of gonadotrophins.

This review aims to evaluate whether severe endometriosis has an impact on the outcome of in vitro fertilisation (IVF), whether IVF is associated with specific complications in this context, whether a specific ovarian stimulation protocol is most appropriate, whether the endometrial condition progresses following ovarian stimulation, and whether endometrial cysts pose a specific problem for IVF. In patients with severe endometriosis, IVF represents an effective treatment option for infertility, as a complement to surgery. The prognostic parameters of IVF are identical to those of other patients. However, the risks related to the severity of endometriosis, particularly the risk of ovarian deficiency, need to be considered. Because of this issue, to which endometriosis-related pain often adds, IVF treatment should be initiated as early as possible, using appropriate protocols and after having fully informed the patient about the specific oocytes retrieval-related risks.

Resume Objectif Le cerclage isthmique par voie abdominale est indique dans les echecs de cerclage par voie vaginale, les pertes fœtales recurrentes du second trimestre et les conisations etendues ou delabrements cervicaux. L’approche cœlioscopique plus recemment decrite doit demontrer, outre sa faisabilite technique, son interet en termes de prevention des accidents obstetricaux. Patientes et methodes Il s’agit d’une evaluation retrospective monocentrique sur 14 cas de cerclage isthmique cœlioscopique selon la technique de Benson, realises hors grossesse entre mai 2005 et novembre 2007. Nous avons analyse les antecedents obstetricaux, les etiologies de beances cervico-isthmiques, les therapeutiques deja mises en œuvre pour leur prise en charge et le devenir de ces patientes apres cerclage. Resultats L’âge moyen des patientes est 33,5 ans. Quatre-vingt-treize pour cent d’entres elles avaient au moins un antecedent d’avortement tardif ou d’accouchement premature et 42,9 % avaient deja eu un echec de cerclage par la technique de Mac Donald. Les indications de cerclage par voie haute ont ete portees dans six cas pour antecedent d’echec de cerclage par voie vaginale et dans huit cas pour impossibilite anatomique du cerclage par voie vaginale. La duree operatoire des cerclages a ete de 45 minutes (35–60 minutes) et la duree d’hospitalisation d’un jour. Aucune complication n’est, a ce jour, survenue en per- ou postoperatoire. Sur les 14 cerclages realises, six ont abouti a une grossesse. Cinq grossesses ont ete menees a terme avec naissance d’enfants vivants. Une grossesse s’est terminee par un avortement spontane du premier trimestre. Discussion et conclusion Le cerclage isthmique par voie cœlioscopique est techniquement realisable et apporte aux patientes les avantages de la cœlioscopie. L’indication doit etre correctement posee et doit repondre aux memes criteres que le cerclage par laparotomie. L’evolution des grossesses cerclees par cette technique semble etre favorable.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 38 - N° S1 - p. F35-F42

Identification of new criteria for embryo quality is required to improve the clinical outcome of in vitro fertilization. The aim of this study was to determine the gene expression profile of cumulus cells (CC) surrounding the oocyte as biomarkers for embryo potential and to identify genes to be used as prognostic indicators of successful pregnancy. CC from single oocytes were analysed using DNA microarrays. Gene expression profiles of CC surrounding the oocyte associated with good embryonic quality and pregnancy outcome were computed. We observed that CC issued from oocytes that developed into embryos with a good morphology had differing gene expression profile according to the pregnancy outcome of the embryo. We demonstrated that the expression of BCL2L11, PCK1 and NFIB in CC is significantly correlated with embryo potential and successful pregnancy. These results were confirmed by quantitative RT-PCR. The gene expression profiling of human CC correlates with embryo potential and pregnancy outcome. BCL2L11, PCK1 and NFIB genes are proposed as biomarkers for predicting pregnancy. Our findings suggest a non-invasive approach, offering a new potential strategy for competent embryo selection. This approach should be validated in single-embryo transfer programmes.

Background Identification of new markers assessing endometrial receptivity may help in improving the clinical outcome of IVF. This study aimed at identifying genes expressed in human endometrium during the implantation window that could be used as such markers. Methods A series of normoresponder patients (n = 31) underwent endometrial biopsies (n = 62, 2 per patient) during the early secretory phase, 2 days after the LH surge (LH + 2) and the mid-secretory phase (LH + 7) of the same natural cycle that preceded a new ICSI attempt for male infertility factor. Samples were analyzed using DNA microarrays and gene expression profiles at the time of the implantation window were computed. Systems biology analysis allowed the identification of biological pathways that were over-represented in this signature. A new approach for class prediction applied to microarray experiments was then used to identify biomarkers putatively involved in endometrial receptiveness. Results Five genes expressed during the implantation window were all up-regulated in the LH + 7 samples compared with LH + 2 [laminin beta3 (P = 0.002), microfibril-associated protein 5 (P = 0.009), angiopoietin-like 1 (P = 0.005), endocrine gland-derived vascular endothelial growth factor (P = 0.049) and nuclear localized factor 2 (P = 0.007)]. Increased expression was validated by quantitative RT-PCR. Conclusions Five genes have been identified for the first time as being up-regulated during the implantation window and are proposed as new biomarkers for exploration of endometrial receptiveness. As the endometrial biopsy procedure can be performed during a natural cycle, it would be worth testing this approach as a novel strategy in patients with poor implantation after IVF or ICSI.

Apoptosis is a cell death program involved in different steps of spermatogenesis, first at puberty, at the beginning of spermatogenesis, then in adult testicles by controlling normal spermatogenesis. As a result, apoptosis deregulation can affect spermatogenesis. Many studies have provided evidence that apoptosis deregulation in germinal cells resulted in male infertility. In addition, apoptosis detection in ejaculated spermatozoa arouses a growing interest in research as a reliable marker of spermatozoon quality. The aim of this review is to summarize our knowledge on physiological apoptosis during spermatogenesis, and then analyse the possibility of using apoptotic markers as selective markers of spermatozoon quality to optimize the rate of success of in vitro fertilization.

Epidemiological evidence clearly shows that obesity contributes to menstrual disorders, infertility and poor pregnancy outcome. Clinicians face two problems: obesity-related infertility and, consequently, obesity in women using assisted reproductive technologies. Whereas weight loss constitutes the first-line therapy for the former, the same does not always apply for the latter. Much debate surrounds the relationship between overweight patients and the outcome of IVF treatment. Adjusting the dose of gonadotropins is the most characteristic feature of IVF treatment in such patients. Nevertheless, considering the poorer outcome of pregnancies in obese patients, all efforts (changes in lifestyle habits, psychological counseling, antiobesity medical therapy and, possibly, bariatric surgery) should be made to encourage weight loss before fertility treatment is begun.

Since the beginning of IVF, natural cycle In Vitro Fertilization (NC-IVF) has been largely replaced by IVF with ovarian stimulation. However, natural cycle IVF has several advantages: low cost, no risk of ovarian hyper stimulation syndrome, very low risk of multiple pregnancy. Nevertheless, natural cycle IVF is less effective with a high risk of cancellation due to premature rise of LH, and an increased risk of failed oocyte retrieval. Using GnRH antagonists in a modified natural cycle decreases the occurrence of a premature LH rise. In the context of a poor responder patient, natural IVF could theoretically yield a better quality oocyte coming from a naturally selected follicle and allow a transfer on an endometrium whose receptivity has not been distorted by controlled ovarian stimulation. However, the real place for it has yet to be defined as we lack published data. Only one randomised controlled study in poor responders showed a similar pregnancy rate to a standard protocol representing a cost-effective alternative. Available retrospective data seem to show the same trend especially in the sub group of younger patients (below 38). Natural cycle IVF is a low-risk, low-cost procedure whose interesting results should be further confirmed by large scale prospective studies.

To examine the outcome of in vitro fertilization according to the body mass index of infertile patients.Between September 2003 and May 2005, 573 patients underwent 789 in vitro fertilization cycles or ICSI because of male factor, tubal factor, and unexplained infertility were retrospectively included from our IVF database. The patients were classified in four groups: BMI20 kg/m2 (264 cycles), 20or = BMI25 (394 cycles), 25or = BMI30 (83 cycles), and BMIor = 30 (48 cycles). All patients had a long protocol for IVF with a combination of the GnRH agonist and recombinant FSH.All parameters of ovarian response were comparable except the total required r-FSH dose. This dose was statistically higher in the group of BMIor = 30 compared to the other groups (p = 0.0003). All parameters of IVF outcome were comparable, including the cancellation rate, the implantation rate, and pregnancy rates.Obese patients require a higher r-FSH dose to achieve follicular maturation than normal weight patients. Obesity does not affect negatively results of in vitro fertilization.

OBJECTIVE: To report a child born with renal impairment following severe anhydramnios due to maternal exposure to an angiotensin II receptor type 1 (AT1) antagonist, valsartan, and hydrochlorothiazide during the first 28 weeks of pregnancy. CASE SUMMARY: A hypertensive woman treated with valsartan 80 mg/day, hydrochlorothiazide 12.5 mg/day, prazosin 10 mg/day, lysine acetylsalicylate 100 mg/day, and levothyroxine 250 μg/day became pregnant. At 28 weeks' gestational age, severe anhydramnios associated with high β2-microglobulin levels in the fetal blood cord was observed. Upon discontinuation of valsartan, fetal renal prognosis improved. In this case, using the Naranjo probability scale, the renal insufficiency of the child was probably related to valsartan. At the age of 2.5 years, the child presented with only mild chronic renal insufficiency. Growth parameters were within the normal range, and there was no evidence of developmental delay. DISCUSSION: Exposure to AT1 antagonists during the second part of pregnancy can lead to abnormalities similar to those observed after exposure to angiotensin-converting enzyme inhibitors, that is, reduced fetal kidney perfusion that may result in oligoamnios and neonatal renal insufficiency. Fourteen previous reports of maternal exposure to AT1 antagonists during this period have been published. In 6 cases, fetal or neonatal death occurred; in 2 cases, pregnancy was terminated because of complete anhydramnios or fetal abnormalities; in 1 case, renal insufficiency persisted at 8 months of age; in 2 cases, kidney function was fairly normal at birth; and in 4 cases, including the one described here, neonatal renal failure improved in the first year of life. CONCLUSIONS: AT1 antagonists should be avoided throughout pregnancy. If these agents are prescribed accidentally to a pregnant woman, monitoring of amniotic fluid volume and β2-microglobulin fetal blood levels after discontinuation of the AT1 antagonist can provide critical data for advising parents on pregnancy and fetal outcome.

The goal for any infertile couple is to explore all reasonable attempts to achieve pregnancy. The couple with infertility resulting from tubal disease has two therapeutic options to achieve this goal: reconstructive tubal surgery and in vitro fertilization. However, the increasing demand for new techniques of assisted reproduction has called into question the value of the more established methods of treatment for tubal infertility. There are some causes of tubal infertility for which surgery has virtually no chance of success. For these situations, in vitro fertilization is clearly the only therapeutic option. For other situations, the decision-making process requires detailed discussion on the effectiveness, adverse effects and cost of the procedures. Endoscopic evaluation of the tubal mucosa is essential for the selective application of tubal surgery. The available evidence shows that tubal surgery can be as, or more, effective as in vitro fertilization for cases of filmy adhesions, mild distal tubal occlusion and proximal obstruction. It may, however, be reasonable to discuss in vitro fertilization with any couple without pregnancy 12 months after tubal surgery. In women with moderate to severe distal tubal disease, the diminishing success rates from surgery suggest that in vitro fertilization should be considered as the first line of treatment. In the case of unsuccessful reconstructive surgery, or if a hydrosalpinx is irreparably damaged, a salpingectomy prior to in vitro fertilization has to be considered. Tubal surgery has indisputable benefits for the patient if infertility is cured by the intervention. A successful tubal repair gives the patient the possibility of conceiving more than once without further treatment. It also gives the couple the psychological advantage of being able to conceive spontaneously. Probably the most pragmatic viewpoint is to consider reproductive surgery and in vitro fertilization as complementary options that are directed towards increasing the overall probability of achieving a pregnancy in the most efficient manner.

We have developed a preimplantation genetic diagnosis (PGD) strategy for Duchenne muscular dystrophy (DMD) allowing the simultaneous amplification of four exons (6, 8, 28 and 32) of the dystrophin gene together with ZFX/ZFY genes for gender determination. Preliminary experiments were carried out on 215 single lymphocytes from male and female individuals. Amplification rates ranged from 90.2% for exon 6 to 96.7% for exons 8 and 32. At least four of the five sequences were successfully amplified in 95.8% of single cells, and sexing was possible in 98.5%. This 5-plex assay was found to be robust enough to be used in a PGD clinical procedure and was therefore applied to a family whose female partner was a heterozygous carrier of a large deletion extending from exon 21 to exon 34 of the dystrophin gene. We have thus analysed two exons located in the deleted region of the gene, two non-deleted exons used as intrasample controls, and ZFX/ZFY genes. Cleavage stage embryo biopsy followed by PCR resulted in transfer of three unaffected embryos. The advantage of the present approach is to identify and subsequently transfer unaffected male embryos in addition to female embryos, and is now applicable to all families displaying a deletion involving at least one of these exons.

Purpose: To evaluate the impact of salpingectomy on therates of embryo implantation and pregnancy in patients withsevere, irreversible tubal factor sterility.

Purpose: Our purpose was to determine the impact of endometrial inflammation on fertility. Methods: The study population included 49 women: 5 women bearing an intrauterine device, 33 sterile patients, and 11 fertile women. Endometrial biopsies were performed between day 17 and day 21 of the cycle. Immunostaining was performed with an ABC kit. Monoclonal antibodies were CD68 for macrophages, CD3 for T lymphocytes, and B-E8 for interleukin (IL)-6; IL-1α and IL-1β were stained with polyclonal antibodies. A double immunofluorescence staining was performed to identify endometrial cells. Macrophage and lymphocyte rates were defined as the percentage of stained cells by field. Double staining was compared among macrophages, T lymphocytes, and anti-IL antibodies in each group. Results: The macrophage rate was high for women bearing an intrauterine device, intermediate for sterile patients, and low for fertile women (P = 0.03). There was a lack of double staining between activated T lymphocytes and anti–IL-6 antibody in tubal sterility and endometriosis. Endometrial macrophages were stained with anti-IL antibodies for all groups. Conclusions: Endometrial macrophages seem to be an interesting parameter for evaluating endometrial inflammation. In tubal infertility and endometriosis, the lack of expression of IL-6 in T lymphocytes could participate in impaired embryo implantation.

Objective: Endometriosis is a painful disease affecting 10–15% of reproductive-age women. Concentrations of several cytokines and angiogenic factors in peritoneal fluid (PF) have been found to correlate with the severity of the disease. However, levels of some analytes vary across the menstrual cycle, and an ideal biomarker of endometriosis has not yet been identified. We have compared the PF concentrations of different cytokines in proliferative and secretory phases in women with and without the disease using the Bio-Plex platform.Methods: PF was aspirated during laparoscopy (N = 133) and the PF concentrations of 18 cytokines from Bio-Plex panels I and II determined with the serum protocol.Results: Increased PF concentrations of IL-6, IL-18, eotaxin, and MCP-1 were found in endometriosis with no changes with menstrual cycle. Levels of IL-12(p70), ICAM-1, and GRO-α were higher in the secretory phase, while eotaxin concentrations were lower.Conclusion: Of the 18 cytokines tested, IL-6, IL-18 and MCP-1 were...

International audience; Background: Reduced uteroplacental perfusion, the initiating event in preeclampsia, is associated with enhanced endothelin-1 (ET-1) production which feeds the vasoconstriction of uterine artery. Whether the treatments of preeclampsia were effective on ET-1 induced contraction and could reverse placental ischemia is the question addressed in this study. We investigated the effect of antihypertensive drugs used in preeclampsia and of ET receptor antagonists on the contractile response to ET-1 on human uterine arteries.Methodology/Principal Findings: Experiments were performed, ex vivo, on human uterine artery samples obtained after hysterectomy. We studied variations in isometric tension of arterial rings in response to the vasoconstrictor ET-1 and evaluated the effects of various vasodilators and ET-receptor antagonists on this response. Among antihypertensive drugs, only dihydropyridines were effective in blocking and reversing the ET-1 contractile response. Their efficiency, independent of the concentration of ET-1, was only partial. Hydralazine, alpha-methyldopa and labetalol had no effect on ET-1 induced contraction which is mediated by both ETA and ETB receptors in uterine artery. ET receptors antagonists, BQ-123 and BQ-788, slightly reduced the amplitude of the response to ET-1. Combination of both antagonists was more efficient, but it was not possible to reverse the maximal ET-1-induced contraction with antagonists used alone or in combination.Conclusion: Pharmacological drugs currently used in the context of preeclampsia, do not reverse ET-1 induced contraction. Only dihydropyridines, which partially relax uterine artery previously contracted with ET-1, might offer interesting perspectives to improve placental perfusion.

A total of 30 years after the first in vitro fertilization (IVF) birth in the world, pregnancy and birth rates following IVF attempts remain low. Indeed, two out of three IVF cycles fail to result in pregnancy, and more than 9 out of 10 transferred embryos fail to implant [1]. Although the selection of high-quality embryos and endometrial status assessment have seen important technological progress, implantation rates are still low after controlled ovarian hyperstimulation (COS) for IVF [2]. Implantation failure is thought to result from impairment of embryo development and/or from abnormal uterine recep tivity. The endometrium is receptive to blastocyst implantation during a spatially and temporally restricted window, ‘the implantation window’ [3]. In humans, this period begins 6–10 days after the lutenizing hormone (LH) surge and lasts approximately 48 h [4,5].

International audience; Total fertilization failures (TFF) are rare events of IVF by intracytoplasmic sperm injection (ICSI). When male factor is excluded, the lack of identifiable aetiological criteria raises the question of the reliable clinical management. The goal of this study was to identify molecular abnormalities in metaphase II (MII) oocytes yielding TFF. The nuclear mature MII oocytes mRNA expression profiles were compared between a 30-year-old patient who had experienced three successive TFF (egg number = 39) and control patients with fertile cohorts diagnosed with tubal or male infertility. The mRNA abundance for the 30,000 genes of the genome was evaluated by microarray and, for selected genes, by quantitative-polymerase chain reaction analysis. Transcriptional analysis of unfertilized MII oocytes revealed an altered gene expression profile associated with TFF. Meiosis, cell growth and apoptosis controlling genes were mis-expressed with important fold changes. The results reveal that, despite passing the pre-IVF morphological examination, high-grade oocytes may carry substantial molecular abnormalities at the gene expression level associated with failure of MII oocyte activation. In the absence of an identifiable defect causing TFF, this microarray approach allows improvement of clinical therapeutic management: informed counselling about alternate therapeutic solutions could be proposed.

In IVF programmes, transvaginal ultrasonography is used as a non-invasive method to evaluate uterine receptivity. The aim of this study was to determine when to perform this investigation in order to optimize prediction of the likelihood of pregnancy. Over 9 months, 124 patients undergoing IVF or intracytoplasmic sperm injection were studied. The ultrasonographic evaluation included endometrial thickness, endometrial pattern, uterine artery pulsatility index, protodiastolic notch, end-diastolic blood flow, and endometrial-subendometrial blood flow distribution pattern. All patients underwent ultrasonographic investigation on the days of human chorionic gonadotrophin (HCG) administration, oocyte retrieval, and embryo transfer. Statistical analysis was done using recursive-partitioning analysis. The pregnancy and implantation rates per transfer were 33 and 19.8% respectively. In terms of single parameters, women with an end-diastolic blood flow, an endometrial-subendometrial blood flow and a multilayered endometrium were more likely to be pregnant than women without one or more of these signs. The most effective combination for evaluation of uterine receptivity was end-diastolic blood flow, endometrial pattern and endometrial thickness. Sensitivity and specificity of this combination were around 81%, positive predictive value was 68.2%, and negative predictive value 89.7%. The best sensitivity and specificity were obtained on the day of HCG administration: respectively 81.1 and 81.3%.

A case is reported of secondary amenorrhoea related to an arteriovenous malformation (AVM) successfully treated with embolization, with a recovery of menstrual cycles. A 28-year-old woman presented with secondary amenorrhoea as the only clinical symptom. Although she had an eugonadic status, there was no genital withdrawal bleeding upon cessation of an oral contraceptive. Pelvic transvaginal ultrasonography revealed a pelvic mass but magnetic resonance imaging (MRI) clearly showed an AVM. Classical angiography was performed with endovascular embolization. Partial thrombosis of the lesion was assessed by magnetic resonance angiography. Recovery of menses occurred 2 months later. It is speculated that blood stolen from the endometrium by the uterine AVM could have been responsible for the amenorrhoea. It is a very unusual cause, and it can be successfully treated with embolization.

Retinoblastoma is a malignant intra-ocular tumour of developing retina initiated by inactivation of both alleles of the retinoblastoma susceptibility (RB1) gene. This paper reports the first clinical experience of preimplantation genetic diagnosis (PGD) for hereditary retinoblastoma using two highly polymorphic microsatellite markers RB1.20 and D13S284, located within and close to the RB1 gene respectively. Duplex PCRs were tested on more than 300 single lymphocytes from heterozygous individuals at both loci, in order to test the accuracy and reliability of the single-cell protocol. This procedure requires a nested PCR and the analysis of fluorescently labelled PCR products on an automatic DNA sequencer. Amplification efficiency and allele drop-out rates ranged from 96.7 to 98.4%, and 3.7 to 5.4% respectively. This test was found to be accurate and reliable enough to be applied to the study of human blastomeres. Subsequently, this approach was used in a PGD treatment cycle for a couple who already had a child affected with hereditary retinoblastoma and found to be informative for both microsatellite markers.

Objective To determine if whole fragments of endometrium can adhere to peritoneum with intact mesothelium. Design Tissue culture and immunohistochemical study. Setting University Medical Center. Patients Reproductive-age women undergoing surgery for benign conditions. Interventions Whole explants of human peritoneum from the anterior abdominal wall and the posterior surface of the uterus were cultured with whole fragments of mechanically dispersed endometrium. Main outcome measures Adhesion of endometrial fragments to the surface of the peritoneum was evaluated. Adherent fragments of endometrium were identified using the dissecting microscope and by performing serial sections of the peritoneum explants for light and confocal laser-scanning microscopy. Immunohistochemical staining of the mesothelium with antibodies to cytokeratin and vimentin was used to ensure an intact layer of mesothelium beneath the endometrial implants. Transmission electron microscopy was also used to evaluate the adhesion of endometrium to the mesothelium. Results Endometrium was identified attached to the surface of the peritoneum. After 18-24 hours of culture, the majority of implants did not have identifiable mesothelium beneath them, but most had intact mesothelium running up to the point of attachment. Approximately 10% of the endometrial implants had intact mesothelium at the site of attachment. After 1 hour of culture, both endometrial stromal and epithelial cells were attached to intact mesothelium in nearly all cases. Early transmesothelial invasion involves endometrial stromal cells. Conclusions Endometrial stromal and epithelial cells can attach to the intact mesothelial surface of the peritoneum. Endometrial stromal cell invasion through the mesothelium occurs in less than 18-24 hours.

Objective: To evaluate the feasability of transvaginal hydrolaparoscopy in infertile patients undergoing basic infertility investigations, and to determine its usefulness in comparison with standard laparoscopy. Materials and methods: Twenty-three unexplained infertile women were prospectively included. Selected patients had no history of pelvic disease or previous pelvic surgery and had normal findings on gynecological examination and vaginal sonography. The patients received general anesthesia and underwent the transvaginal hydrolaparoscopy immediately prior to a standard laparoscopy by a different operator. The main outcome measures were the rate of successful access to the pouch of Douglas, the duration of the procedure, and the rate of complications. In order to compare the accuracy of the transvaginal hydrolaparoscopy to the standard laparoscopy, findings in terms of tubal pathology, endometriosis, and adhesions were analyzed. Results: The successful rate of access to the pouch of Douglas was 95.7%. The rate of complications was 4.3%. The mean duration of the transvaginal hydrolaparoscopy procedure was 8 min. The concordance between transvaginal hydrolaparoscopy and laparoscopy for pelvic cavity examination was statistically significant ( k =0.57, P =0.02). In 40.9% of cases, the transvaginal hydrolaparoscopy procedure has shown a normal pelvic examination confirmed by laparoscopic diagnosis. According to the findings by laparoscopy, transvaginal hydrolaparoscopic diagnosis was correlated well in 81.8% of cases. When transvaginal hydrolaparoscopy showed pathological findings, there were no normal laparoscopies. Pathological laparoscopies were found in 18.2% of the normal transvaginal hydrolaparoscopies. Conclusion: The transvaginal hydrolaparoscopy is a reproducible and safe method to investigate the pelvis and its structures. The diagnostic accuracy of the transvaginal hydrolaparoscopy suggests that more than 40% of standard laparoscopies for unexplained infertility could be avoided.

The aim of this study was to compare the outcome of triplets managed expectantly or by multifetal reduction to twins to assess the potential benefit of fetal reduction. The study design was prospective, comparative and monocentric and the study was conducted in a teaching hospital. Out of 148 women with triplets mostly obtained after infertility treatment, 83 were expectantly managed while 65 chose reduction to obtain twins. Main outcome measures were fetal loss before 24 weeks, premature deliveries before 28, 32 and 34 weeks, rate of low birthweight infants and neonatal and perinatal mortality rates. The fetal loss rate before 24 weeks did not differ between the ongoing group and the reduced group (6 versus 5.4%). Reducing triplets was associated with a significantly lower incidence of the following: prematurity before 28, 32 and 34 weeks (P < 0.001), low birthweight infants whose weights were under the third centile (P < 0.002) and infants whose weights were less than 1000, 1500 and 2000 g (P < 0.001). Neonatal (although apparently lower in the reduced group) and perinatal mortality did not significantly differ. Our results indicate that reduction of triplets to twins is effective to improve preterm birth and fetal growth.

The aim of this study was to evaluate the feasibility of routine falloposcopy in infertile patients undergoing basic infertility investigations, and to determine its usefulness in comparison with other tubal investigation methods. Seventy-five infertile women were selected based on the following criteria: 2 years of infertility, age between 18 and 40 years, normal ovulation, and partner with normal spermatozoa. Based on the results of the classical means of tubal evaluation (hysterosalpingography and laparoscopy), these patients were classified in one of two groups: tubal or unexplained infertility. All patients underwent a falloposcopy under general anaesthesia. The procedures were performed by the same surgeon with the linear everting catheter. Based on the falloposcopic findings, these patients were then reclassified in one of two other groups: falloposcopic tubal or falloposcopic unexplained infertility. The mean outcome measures were catheterization rate, duration of the procedure, pregnancy rates, complication rate and predictive value of Falloposcopy. The tubal catheterization rate was 94.5%. The mean duration of falloposcopy was 19 min per tube. Based on a standard scoring system, the spontaneous pregnancy rates were 27.6% for a score20; 11.5% for a score between 21 and 30; and 0% if the score was30. Complication rate was 5.1% of pinpoint perforations of the tube. With Cox's statistical model, none of the parameters analysed was statistically predictive of intrauterine pregnancy. We conclude that the greater accuracy of diagnosis by falloposcopy may indicate that it should be incorporated into the initial screening of infertile patients.

Objective: To evaluate the implantation rate and pregnancy rate (PR) in patients with severe tubal factor infertility who were undergoing IVF. Patients who had undergone salpingectomy were compared with those who had not. Design: A prospective randomized study. Setting: A department of obstetrics and gynecology at a university hospital. Patient(s): Thirty patients who previously had undergone salpingectomy and 30 patients who had not undergone salpingectomy before IVF treatment. Intervention(s): Laparoscopy with or without salpingectomy followed by IVF with the use of combined GnRH agonist and hMG therapy in a long stimulation protocol. Main Outcome Measure(s): Embryo implantation rate and ongoing PR per transfer. The cumulative PRs were compared for the two groups of patients. Result(s): After the first IVF attempt, the implantation rate was 10.4% in the group with salpingectomy and 4.6% in the group without salpingectomy. For all IVF attempts, the respective embryo implantation rates in the two groups were 13.4% and 8.6%. The ongoing PR per transfer was 34.2% in the group with salpingectomy compared with 18.7% in the group without salpingectomy. After four IVF attempts, the probability of becoming pregnant was greater in the group of patients with salpingectomy (75%) than in the group without salpingectomy (63%). Conclusion(s): Previous salpingectomy in patients with severe tubal factor infertility who are undergoing IVF seems to increase the embryo implantation rate and the PR per cycle of IVF. This monocentric study must be followed by other similar studies to allow for a metaanalysis and confirm this clear trend with definitive evidence.

Objective: To present a case of IVF–surrogate pregnancy in a patient with ovarian transposition who had undergone chemotherapy and total pelvic irradiation. Design: Case report. Setting: Teaching hospital. Patient(s): A 29-year-old woman who had undergone Wertheim's hysterectomy for a bulky carcinoma of the uterine cervix. Intervention(s): Ovarian transposition before chemotherapy and total pelvic irradiation. Standard IVF treatment, transabdominal oocyte retrieval, and transfer to the surrogate mother. Main Outcome Measure(s): Results of the IVF cycle. Result(s): A twin pregnancy at the first cycle and two live newborns. Conclusion(s): This is the first reported case of ovulation induction and oocyte retrieval performed on a transposed ovary.