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

L'accueil d'embryon (une technique récente d'assistance médicale à la procréation)

La mise au point des techniques de congélation embryonnaire a permis une meilleure prise en charge des couples suivis en FIV, en limitant le nombre d embryons transférés et diminuant ainsi le risque de grossesses multiples. Mais cette congélation embryonnaire crée une dissociation dans le temps entre le projet parental et sa réalisation avec pour conséquence possible une disparition de ce projet. Ces embryons surnuméraires posent dès lors des questions spécifiques quant à leur devenir. La question du statut de l embryon humain prend ici toute son importance. L'accueil d'embryon par un couple infertile receveur représente depuis 1999, un des choix offerts aux couples qui disposent d'embryons congelés pour lesquels ils n'ont plus, à titre personnel, de projet parental. En pratique, cette nouvelle possibilité d'assistance médicale à la procréation est assez peu réalisée en France depuis son autorisation alors qu elle ne présente pas de problème technique particulier. Cette relative désaffection des professionnels semble plutôt le fait de problèmes d organisation aggravés par un encadrement législatif particulièrement pointilleux. Cependant certains en refusent le principe pour des raisons éthiques. De nombreuses restent en suspens quant au devenir de l enfant né par cette technique qui crée une rupture totale de filiation biologique tout en maintenant un lien gestationnel. Le principe de l'anonymat qui encadre cette pratique impose à l enfant le secret de ses origines génétiques. La traçabilité des données concernant les embryons est indispensable. Bien que les premières données soient rassurantes, le suivi des familles d'origine des familles d accueil d embryon et des enfants nés est nécessaire pour évaluer les difficultés éventuelles pouvant survenir à long terme. L'équipe d'AMP du CHU d'Amiens vient de mettre en place cette activité. Les premières données recueillies sont comparables aux données obtenues dans les quelques centres ayant débuté l'accueil d'embryon.AMIENS-BU Santé (800212102) / SudocSudocFranceF

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

Follicular GH and IGF1 Levels Are Associated With Oocyte Cohort Quality: A Pilot Study

International audienceIntroductionOocyte quality contributes to the development of an optimal embryo and thus a successful pregnancy. The objective of this study was to analyse the association between oocyte cohort quality and the follicular levels of growth hormone (GH), insulin-like growth factor 1 (IGF1), 25-hydroxy vitamin D (25OHD), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and antithyroid antibodies, as a function of intracytoplasmic sperm injection (ICSI) outcomes. Material and methodsWe conducted a prospective comparative pilot study from January 2013 to December 2017. 59 ICSI cycles constituted an abnormal oocyte cohort (n=34 cycles, in which more than 50% of oocytes presented at least one morphological abnormality) and a normal oocyte cohort (n=25 cycles, in which 50% or less of the oocytes presented at least one morphological abnormality). GH, IGF1, 25OHD, TSH, fT3, fT4 and antithyroid antibodies were measured in follicular fluid. ResultsThe fertilisation rate was lower in the abnormal oocyte cohort (65.5% vs. 80%, respectively, p=0.012). Oocytes' proportion with at least one abnormality was 79.4% in the abnormal oocyte cohort and 29.0% in the normal oocyte cohort. The mean number of morphological abnormalities per oocyte was significantly higher in the abnormal oocyte cohort. The follicular levels of GH (4.98 vs. 2.75 mIU/L, respectively; p <0.01) and IGF1 (72.1 vs. 54.2 ng/mL, respectively; p=0.05) were higher in the normal oocyte cohort. There was no association with follicular levels of TSH, fT3, fT4, antithyroid antibodies, or 25OHD. ConclusionOocyte cohort quality appears to be associated with follicular levels of GH and IGF1

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

Impact of oocytes with CLCG on ICSI outcomes and their potential relation to pesticide exposure

Abstract Background Oocyte quality is a key limiting factor in female fertility which is primarily reflected in morphological features. Centrally located cytoplasm granulation (CLCG) is one type of cytoplasmic dimorphism exhibited by oocytes that could be linked to pesticide exposure with a significant risk of decreased ICSI outcomes. Methods This retrospective study included 633 women who were part of an intracytoplasmic spermatozoa injection (ICSI) program between 2009 and 2011. The participants lived in the Picardy region of France and had been exposed to pesticides. The participants were divided in two groups based on prevalence of oocytes with CLCG (LCLCG [n = 83]: low prevalence of oocytes with CLCG under 25%. HCLCG [n = 68]: high prevalence of CLCG over 75%). The embryological and clinical outcomes were analysed for both groups and were calculated using the difference between the two values. Results Results for couples with HCLCG compared to LCLCG showed a decrease in embryo cleavage, ongoing pregnancy, and live birth rates (82%, 14%, 13% vs 99%, 32%, 30%, respectively).The early miscarriage rate was increased (47% vs 11%), with an OR of 3.1 (95%CI [2.1–4.1]). Due to high pesticide exposure (over 3000 g/ha), there is a higher risk of a resulting disturbed oocyte cohort with a high prevalence of CLCG over 75%. Conclusion The high prevalence of oocytes with CLCG over 75% has a negative effect on embryos and the general ICSI clinical outcomes. Furthermore, a putative association between pesticide exposure and risk of CLCG was identified, justifying the need for further research and a potential need to find alternative assisted reproductive technologies for these couples. Trial registration Tabacfertimasc. ID number: ID2011-A00634–37 ; registered 2011/2/