Physiopathology of human embryonic implantation: clinical incidences.

Embryo implantation consists of a series of events promoting the invasion of the endometrium and then the uterine arterial system by the extra-embryonic trophoblast. In order for this semi-heterologous implantation to succeed, the endometrium has to first undergo a number of structural and biochemical changes (decidualization). The decidua's various constituents subsequently play a role in the embryonic implantation. The third step is the transformation of the uterine vascular system and the growth of the placenta, which will provide the foetoplacental unit with nutrients. Several physiopathological aspects will be discussed: 1) the implantation window, regulated by maternal and embryonic hormonal secretions and thus influenced by any defects in the latter: dysharmonic luteal phase, 21-hydroxylase block, abnormal integrin expression, 2) the successive trophoblast invasions of uterine vessels which, when defective, lead to early embryo loss or late-onset vascular pathologies, as preeclampsia, 3) the pregnancy's immunological equilibrium, with a spontaneously tolerated semi-allogeneic implant, 4) the impact of pro-coagulant factors (thrombophilia) on the pregnancy's progression, 5) the environment of the uterus, ranging from hydrosalpinx to uterine contractions. In summary, the least anatomical or physiological perturbation can interfere with human embryonic implantation - a very particular phenomenon and a true biological paradox

Les limites du dépistage de la trisomie 21 en Picardie (à propos de 30 cas entre 2009 et 2011)

Introduction : La trisomie 21 est la plus fréquente des anomalies chromosomiques. Les recommandations de l HAS de juin 2007 ont fixé les règles du dépistage de la trisomie 21. Le texte organisant et réglementant le dépistage combiné a été publié au Journal Officiel du 3 juillet 2009 (arrêté du 23 juin 2009). Objectifs : Notre étude a analysé de façon rétrospective 30 cas de trisomie 21, diagnostiqués en période post-natale et nés en Picardie entre 2009 et 2011. Le but est d évaluer les défaillances du dépistage de la trisomie 21 mis en place dans notre région. Résultats : Nous avons retrouvé une incidence de 1/2532 trisomie 21 non diagnostiquées en période prénatale en 2009, 1/2838 en 2010 et 1/1757 en 2011. 10% des patientes n avaient bénéficié d aucun dépistage. 33% des patientes avaient bénéficié d une échographie de dépistage du 1er trimestre seule. 13% des patientes avaient eu recours à un dosage des marqueurs sériques du 2ème trimestre seul. 27% des patientes avaient eu un dépistage séquentiel non intégré. 10% des patientes avaient bénéficié d un dépistage séquentiel intégré et seulement 7% d un dépistage combiné du 1er trimestre. Notre population compte 10 cas de faux négatifs du dépistage. Pour 70% d entre eux a été réalisé un dépistage séquentiel non intégré, pour 20% un dépistage séquentiel intégré et pour 10% un dépistage combiné du 1er trimestre. Conclusion : Le taux de faux négatifs du dépistage apparaît difficilement réductible. L échographie du 1er trimestre reste le maillon faible. Par ailleurs, il semble nécessaire d insister sur l importance de l information devant accompagner les différentes étapes du dépistage. L arrêté du 23 juin 2009 est l aboutissement de ces décennies d évolution des techniques biochimiques et échographiques. La mise en place du dépistage combiné est par conséquent le point de départ d une nouvelle décade de dépistage prénatal.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Comparison of two preventive treatments for patients with recurrent miscarriages carrying a C677T methylenetetrahydrofolate reductase mutation: 5-year experience

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Comparative prospective study of 2 ovarian stimulation protocols in poor responders: effect on implantation rate and ongoing pregnancy

International audienceBackground: In patients treated with IVF, the incidence of poor ovarian response (POR) after ovarian stimulation varies from 9 to 25 %. However, at present, there are no clear guidelines for treating these poor responders. This study was designed to compare two different ovarian stimulation protocols and addresses future perspectives in the management of these unfortunate patients. Method: Four hundred and forty poor responders were studied during their second IVF cycle. They had all failed to become pregnant during their first IVF cycle where the long GnRH-agonist stimulation protocol (P1) was used. Patients were prospectively randomly assigned to 2 protocol groups (P2 or P3, 220 patients in each arm) at the start of ovarian stimulation according to the order of entry into the study including one patient per each stimulation protocols: The P2 group was treated with a contraceptive pill + flare-up GnRH-agonist protocol and the P3 group with the GnRH-antagonist protocol. The ovarian stimulation characteristics as well as the clinical and ongoing pregnancy rates were compared. Result(s): Although the numbers of embryos obtained and transferred were significantly higher with the P2 protocol, the implantation and ongoing pregnancy rates per transfer were the same in the two studied groups (8.9 % versus 14.6 % and 8.4 % versus 14.2 % for the P2 and P3 protocols, respectively). Good prognostic factors for ongoing pregnancy with both protocols were: a maternal age 10 mm. Conclusion(s): In poorly responding patients treated with IVF, the implantation and ongoing pregnancy rates per transfer were not significantly different between the two protocols studied: contraceptive pill + flare-up GnRH-agonist protocol and the GnRH-antagonist protocol. It is suggested that current strategies for the management of poor responders be reconsidered in the light of the potential contribution of age and the effect of life style changes on fertility potential. A customised policy of ovarian stimulation in these patients including mild stimulation protocols, sequential IVF cycles, oocytes-embryos freeze all protocols and blastocyst transfers after screening may improve the clinical outcome

Physiopathology of human embryonic implantation: clinical incidences.

Embryo implantation consists of a series of events promoting the invasion of the endometrium and then the uterine arterial system by the extra-embryonic trophoblast. In order for this semi-heterologous implantation to succeed, the endometrium has to first undergo a number of structural and biochemical changes (decidualization). The decidua's various constituents subsequently play a role in the embryonic implantation. The third step is the transformation of the uterine vascular system and the growth of the placenta, which will provide the foetoplacental unit with nutrients. Several physiopathological aspects will be discussed: 1) the implantation window, regulated by maternal and embryonic hormonal secretions and thus influenced by any defects in the latter: dysharmonic luteal phase, 21-hydroxylase block, abnormal integrin expression, 2) the successive trophoblast invasions of uterine vessels which, when defective, lead to early embryo loss or late-onset vascular pathologies, as preeclampsia, 3) the pregnancy's immunological equilibrium, with a spontaneously tolerated semi-allogeneic implant, 4) the impact of pro-coagulant factors (thrombophilia) on the pregnancy's progression, 5) the environment of the uterus, ranging from hydrosalpinx to uterine contractions. In summary, the least anatomical or physiological perturbation can interfere with human embryonic implantation - a very particular phenomenon and a true biological paradox

Predictive factors for pregnancy after intrauterine insemination (IUI): An analysis of 1038 cycles and review of the literature. Fertil Steril

Objective: To determine the predictive factors for pregnancy after IUI. Design: Retrospective study. Setting: A single university medical center. Patient(s): One thousand thirty-eight IUI cycles in 353 couples were studied between 2002 and 2005. Intervention(s): Ovarian stimulation via SC injection of FSH or hMG was performed daily; IUI was then performed 36 hours after triggering ovulation if at least one follicle measuring >16 mm and an endometrial thickness of >7 mm (with triple-line development) were obtained. Main Outcome Measure(s): Clinical pregnancy rates were analyzed according to the woman's age, the type of infertility, the spermogram characteristics, the total motile spermatozoa (TMS) count, the E 2 level before hCG injection, and the number of mature follicles. Result(s): The couple with the best chance of pregnancy can be described as follows: an under 30 woman with cervical or anovulatory infertility and a man with a TMS R5 million spermatozoa. The ''ideal'' stimulation cycle enables the recruitment of two follicles measuring >16 mm with an E 2 concentration >500 pg/mL on the day of hCG administration. The best results are obtained when IUI is performed using a soft catheter. Conclusion(s): This study enabled the characterization of many prognostic factors for pregnancy and particularly those for women at risk of multiple pregnancies after IUI. (Fertil Steril Ò 2010;93:79-88 At present, 16% of prospective parents seek medical advice for infertility. Some of these couples will need to undergo IUI using the prospective father's fresh sperm. This method of assisted reproductive technology is indicated in cases of cervical infertility, relative male factor infertility, anovulation, endometriosis with a healthy fallopian tube, and, lastly, unexplained infertility. In the literature, many factors have been reported as influencing pregnancy rates after IUI: the woman's age, the length of infertility, indications (type of infertility), the sperm count in the initial analysis or in the catheter, the number of mature follicles, the E 2 concentration on the day of hCG administration, and the type of catheter used. However, the various investigators have not agreed on the nature and ranking of these criteria. In France, the clinical pregnancy rate per IUI cycle is only 11.8%, and the rate of childbirth per cycle is below 9% (1). The aim of this retrospective study was to report on 4 years of IUI practice (1038 cycles) at Amiens University Medical Center and determine the predictive factors for successful pregnancy and birth. MATERIALS AND METHODS Before each course of treatment, the following tests were performed: hysterosalpingography, serum hormone assays on the third day of the menstrual cycle (estradiol-17b, FSH, LH, and PRL), semen analysis (notably the total motile spermatozoa [TMS] count), and a postcoital test (H€ uhner's test). After centrifugation of a semen sample in a discontinuous density gradient column (Puresperm, Nidacon, M€ olndal, Sweden), the TMS count was obtained by multiplying the total sperm count by the prewash percentage of mobility. Sperm morphology was rated according to the World Health Organization (WHO) criteria (2). IUIs with donor sperm were excluded from the present study. The postcoital test was positive when more than 10 motile spermatozoa were observed in the endocervical sample with an Insler score >10. If the postcoital test remained negative despite the administration of additional vaginal estrogens or ovarian stimulation (i.e., cervical infertility), then IUI was considered to be appropriate

Effect of Gonadotropin Types and Indications on Homologous Intrauterine Insemination Success: A Study from 1251 Cycles and a Review of the Literature

Objective. To evaluate the IUI success factors relative to controlled ovarian stimulation (COS) and infertility type, this retrospective cohort study included 1251 couples undergoing homologous IUI. Results. We achieved 13% clinical pregnancies and 11% live births. COS and infertility type do not have significant effect on IUI clinical outcomes with unstable intervention of various couples’ parameters, including the female age, the IUI attempt rank, and the sperm quality. Conclusion. Further, the COS used seemed a weak predictor for IUI success; therefore, the indications need more discussion, especially in unexplained infertility cases involving various factors. Indeed, the fourth IUI attempt, the female age over 40 years, and the total motile sperm count <5 × 106 were critical in decreasing the positive clinical outcomes of IUI. Those parameter cut-offs necessitate a larger analysis to give infertile couples more chances through IUI before carrying out other ART techniques

Can Ratios Between Prognostic Factors Predict the Clinical Pregnancy Rate in an IVF/ICSI Program with a GnRH Agonist-FSH/hMG Protocol? An Assessment of 2421 Embryo Transfers, and a Review of the Literature

International audienceNone of the models developed in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is sufficiently good predictors of pregnancy. The aim of this study was to determine whether ratios between prognostic factors could predict the clinical pregnancy rate in IVF/ICSI. We analyzed IVF/ICSI cycles (based on long GnRH agonist-FSH protocols) at two ART centers (the second to validate externally the data). The ratios studied were (i) the total FSH dose divided by the serum estradiol level on the hCG trigger day, (ii) the total FSH dose divided by the number of mature oocytes, (iii) the serum estradiol level on the trigger day divided by the number of mature oocytes, (iv) the serum estradiol level on the trigger day divided by the endometrial thickness on the trigger day, (v) the serum estradiol level on the trigger day divided by the number of mature oocytes and then by the number of grade 1 or 2 embryos obtained, and (vi) the serum estradiol level on the trigger day divided by the endometrial thickness on the trigger day and then by the number of grade 1 or 2 embryos obtained. The analysis covered 2421 IVF/ICSI cycles with an embryo transfer, leading to 753 clinical pregnancies (31.1% per transfer). Four ratios were significantly predictive in both centers; their discriminant power remained moderate (area under the receiver operating characteristic curve between 0.574 and 0.610). In contrast, the models' calibration was excellent (coefficients: 0.943-0.978;p < 0.001). Our ratios were no better than existing models in IVF/ICSI programs. In fact, a strongly discriminant predictive model will be probably never be obtained, given the many factors that influence the occurrence of a pregnancy