Lionel Reyftmann

Effects of cigarette smoking on reproduction

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.

Synechia after uterine compression sutures.

We present a study of 37 women who underwent uterine compression suture for postpartum hemorrhage, with 13 postoperative assessments by hysteroscopy. Synechia occurred in seven patients, of whom three had Asherman syndrome (23% of women who desired pregnancy and had hysteroscopic evaluation) that could not be corrected.

Optimal timing of ultrasonographic and Doppler evaluation of uterine receptivity to implantation

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%.

Total fertilization failure and molecular abnormalities in metaphase II oocytes.

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.

Endometriosis and in vitro fertilisation: a review

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.

Myotonic dystrophy type 1 and PGD: ovarian stimulation response and correlation analysis between ovarian reserve and genotype.

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 centres 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, P<0.001) 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.

Do female translocations influence the ovarian response pattern to controlled ovarian stimulation in preimplantation genetic diagnosis

BACKGROUND Ovarian response in female translocation carriers is not well understood. We aimed to evaluate the impact of chromosomal autosomal balanced translocations on the ovarian response to controlled ovarian stimulation (COS) in female carriers undergoing IVF and PGD. METHODS In a retrospective study, we included all female translocation carriers who underwent PGD at our centre. We compared these patients to female patients from couples with male translocation carriers who underwent PGD. RESULTS Results from 79 cycles of PGD from 33 female translocation carriers were compared with 116 cycles from 55 male translocation carriers. No difference was observed for patient characteristics: female age, anti-Müllerian hormone or antral follicle count. No difference in COS parameters was observed for the total dose of recombinant FSH, the number of retrieved oocytes and embryos on Day 3, for unaffected and transferred embryos. For the two groups, pregnancy rate was similar per cycle (12.7 versus 20.7%, P = 0.208). Multivariate analysis demonstrated that female translocation carriers had a significantly higher estradiol level on the day of hCG administration (+540 pg/ml, P = 0.05). CONCLUSIONS This paper is the largest to report ovarian response of female translocation carriers. This study showed that the ovarian response to COS was not impaired by balanced translocation status, suggesting that female chromosomal structural abnormalities did not influence the results of COS in PGD. Thus, female carriers of balanced translocations could be considered normal responders and standard doses of gonadotrophins used for ovarian stimulation.

Anterior approach to laparoscopic uterine artery ligation.

Herein is described an anterior approach to uterine artery ligation during laparoscopic myomectomy and total laparoscopic hysterectomy. The anterior leaf of the broad ligament is opened and the uterine artery is clipped lateral to its crossing over the ureter. Outcome measures were completion of the procedure laparoscopically and the need for transfusion postoperatively. Thirty-eight myomectomies and 28 difficult total laparoscopic hysterectomies (primarily uteri with large myomas) were performed, with 1 conversion to laparotomy during myomectomy and 1 during hysterectomy, and 1 transfusion after total laparoscopic hysterectomy. The anterior approach to uterine artery ligation is an alternative method for treatment of uterine artery occlusion during laparoscopic myomectomy or hysterectomy performed to treat large myomas.

Solutions thérapeutiques pour les infertilités masculines

La part de l’homme dans les causes de l’infertilité du couple, a été depuis la nuit des temps, sous estimée dans toutes les sociétés. Nous avons pensé pendant longtemps que la femme était le plus souvent tenue pour responsable de la stérilité du couple. C’est la femme qui procrée ! On considère qu’elle n’est pas enceinte, c’est donc elle est stérile. En effet, la responsabilité seule de la femme n’apparaît que dans 30 % des cas, celle de l’homme dans 30 % des cas et dans 40 % où les sont responsables. Ainsi, annoncer à l’homme les résultats d’azoospermie après un spermogramme, est, non seulement un véritable drame intérieur, mais aussi et surtout une catastrophe familiale. Heureusement, les récents progrès en AMP sont venus atténuer ce drame et redonner de l’espoir. Cependant, depuis une trentaine d’années, la part de l’infertilité masculine ne cesse de croître. Concernant la fréquence actuelle des infertilités masculines, trois facteurs pourraient être responsables de leur apparente augmentation : l’âge plus avancé du père dans les procréations des couples, une meilleure détection du nombre des infertilités en rapport avec des causes connues ou récemment découvertes, ou enfin une altération de la qualité du sperme. Malgré de multiples essais thérapeutiques, le traitement médical de l’infertilité masculine in vivo reste décevant. À l’exception des traitements antibiotiques ou anti-inflammatoires, le traitement par les gonadotrophines dans le cadre des insuffisances gonadotropes demeure la seule indication médicale de l’infertilité masculine. L’assistance médicale à la procréation (AMP) constitue aujourd’hui le seul recours au traitement de l’infertilité masculine. Les techniques d’AMP ne représentent pas un traitement curatif de l’infertilité masculine mais, une démarche thérapeutique permettant aux couples infertiles de réaliser leur projet parental. Les techniques de préparation du sperme in vitro en vue d’une AMP ont pour but d’éliminer le plasma séminal, les débris cellulaires et les spermatozoïdes immobiles et de sélectionner des spermatozoïdes mobiles et à morphologie normale. En fait, les techniques de préparation du sperme in vitro tendent à mimer le rôle de la glaire cervicale. Les deux techniques les plus communément utilisées sont la migration ascendante (swim-up) suivi d’un lavage, et la centrifugation sur gradient de densité (pure sperm). La première technique est principalement recommandée lorsque la mobilité des spermatozoïdes est préservée. Pour le pure sperm, elle est particulièrement utilisée pour un sperme ayant une oligo-asthéno-tératospermie modérée ou sévère. Le choix entre les différentes techniques d’AMP disponibles dans la prise en charge de l’infertilité masculine repose essentiellement sur le nombre de spermatozoïdes mobiles et à morphologie normale récupérés après préparation du sperme in vitro. C’est ainsi que progressivement la pratique de l’insémination artificielle (IA), en suite la FIVc et plus récemment la fécondation in vitro par micro injection ovocytaire (ICSI), ont complètement changé la prise en charge de l’infécondité masculine dans son ensemble et celle de l’azoospermie en particulier. L’insémination artificielle avec le sperme du conjoint (IAC) a été préconisée dès la fin du 18e siècle et la congélation des spermatozoïdes n’a eu lieu qu’au milieu du 20e siècle

Amenorrhoea revealing an arteriovenous uterine malformation, and recovery of menses after embolization

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.