[Etiology of preeclampsia after assisted reproductive treatments]. / Étiologie de la prééclampsie après traitements de procréation médicalement assistée.

About 12 percent of women require assisted reproductive technology (ART) to get pregnant as infertility concerns more and more couples. Recent studies highlight obstetrical complications after ART such as preeclampsia, gestational diabetes or placenta accrete spectrum. Pre-eclampsia is a specific pathology of the pregnancy which can lead to materno-fetal complications including prematurity and intrauterine growth restriction. The aim of this article is to summarize preeclampsia risk factors during ART. We performed a narrative review based on articles published since 2010. Preeclampsia rate is increased after frozen embryo transfer, especially in case of artificial cycle, multiple pregnancies and gamete donation.

Environ 12 % des femmes dans le monde auront recours aux techniques de procréation médicalement assistée (PMA) pour concevoir. L'infertilité concerne de plus en plus de couples. Des études récentes mettent en évidence des complications obstétricales après la PMA telles que la prééclampsie, le diabète gestationnel et le spectre des placenta accreta. La prééclampsie est une pathologie spécifique de la grossesse qui peut entraîner des complications materno-fœtales, notamment la prématurité et le retard de croissance intra-utérin. L'objectif de cet article est de résumer les facteurs de risque de la prééclampsie liés à la PMA. Nous avons réalisé une revue narrative basée sur les articles publiés depuis 2010. Le taux de prééclampsie est augmenté après les transferts d'embryons congelés, en particulier en cas de cycle artificiel, de grossesses multiples, de don de gamètes et d'hyperstimulation ovarienne.

[La dyspareunie féminine, not a simple functional disorder !] / La dyspareunie féminine, pas un simple trouble fonctionnel !

Dyspareunia is defined as pain during sexual intercourse. It will be qualified as superficial if it occurs during the vaginal penetration and as deep when it appears in the lower abdomen or further in the vagina. It concerns between 10 and 28 % of women during their lifetime and will have a significant impact on their quality of life. Multidisciplinary care will allow an accurate diagnosis and optimal treatment. The collaboration between general practitioner, gynecologist, physiotherapist and psychologist is mandatory in order to improve the quality of life of patients.

La dyspareunie se définit par une douleur lors du rapport sexuel. Elle sera qualifiée de superficielle si elle survient lors de la pénétration du vagin, et de profonde lorsqu'elle apparaît lors de la pénétration complète et est décrite dans le bas du ventre ou dans le fond du vagin. Elle concerne entre 10 et 28 % des femmes au cours de leur vie et impactera de manière importante leur qualité de vie. Une prise en charge multidisciplinaire permettra un diagnostic précis et un traitement optimal. La collaboration entre médecin traitant, gynécologue, physiothérapeute et psychologue est une condition sine qua non pour l'amélioration de la qualité de vie des patientes.

Impact of Adenomyosis and Endometriosis on Chronic Pelvic Pain after Niche Repair.

Chronic pelvic pain (CPP) is one of the main isthmocele symptoms, together with abnormal uterine bleeding and secondary infertility. When patients undergo a laparoscopic niche repair surgery, it is important to determine if they present associated pathologies, such as adenomyosis and/or endometriosis, which are also a cause of CPP. A retrospective study was performed on 31 patients with CPP undergoing a laparoscopic niche repair. The pre-operative ultrasound was analyzed to determine the presence of adenomyosis. Endometriosis was histologically diagnosed. CPP outcome was evaluated at early (3-6 months) and late (12 months) post-operative follow ups. In our population of 31 women presenting CPP, only six of them (19.4%) did not have any associated pathology. In the group of 25 patients with associated pathology, 10 (40%) had no benefit from the reconstructive surgery in terms of CPP at early follow-up (3-6 months) and 8 (32%) in the post-operative period at 12 months. Patients with CPP who undergo niche repair should be carefully selected as CPP does not seem to be a good indication for uterine scar repair in patients with concomitant adenomyosis and endometriosis.

Implantation Failure in Endometriosis Patients: Etiopathogenesis.

Embryo implantation requires adequate dialogue between a good quality embryo and a receptive endometrium. This implantation is still considered as the black box of reproductive medicine. Endometriosis is a highly prevalent chronic inflammatory disease, concerning about 10% of women of reproductive age and is one of the major causes of female infertility. The mechanisms involved in endometriosis-related infertility, an event not yet completely understood, are multifactorial and include anatomical changes, reduction in ovarian reserve, endocrine abnormalities, genetic profile, immunity markers, inflammatory mediators, or altered endometrial receptivity. In this article, we will focus on the impact of endometriosis on embryo quality and on endometrial receptivity. Results: Poor oocyte and embryo quality seem to promote a lower pregnancy rate, more than the endometrium itself in women with endometriosis. Other studies report the contrary. In addition, hormonal imbalance observed in the endometrium could also alter the embryo implantation. Conclusions: Controversial results in the literature add difficulties to the understanding of the mechanisms that lead to embryo implantation disorders. Furthermore, either oocyte/embryo impairment, altered endometrium, or both may cause impaired implantation. New prospective, randomized, and controlled studies are necessary to determine the origin of the defects that make conception more difficult in the case of endometriosis and adenomyosis.

Oocyte Cryopreservation in Patients with Endometriosis: Current Knowledge and Number Needed to Treat.

The rise of oocytes cryopreservation (OOC) in assisted reproductive techniques allows fertility preservation (FP) in an increasing number of indications. Endometriosis, a highly prevalent disease, potentially impairing ovarian reserve, seems, therefore, an interesting indication for it. The purpose of this study is to summarize the available evidence concerning FP by OOC in women with endometriosis and to calculate the number needed to treat (NNT). In total, 272 articles related to this topic were identified in PubMed. Eight studies were eligible for the review. In order to shed some light, a SWOT analysis was performed and the argument pros and cons were developed. The NNT calculated of OOC was 16, meaning that 16 women need to perform an OOC for one of them to have a child that she would not have had without this technique. In conclusion, OOC must be discussed with patients who suffer from endometriosis since it is an effective technique of FP, which can allow these patients to succeed a pregnancy that they otherwise would not have achieved. Nevertheless, it should not be performed in all patients as there is still a lack of robust socio-economic and risk-benefit data.

The steroid hormone estriol (E3) regulates epigenetic programming of fetal mouse brain and reproductive tract.

BACKGROUND: Estriol (E3) is a steroid hormone formed only during pregnancy in primates including humans. Although E3 is synthesized at large amounts through a complex pathway involving the fetus and placenta, it is not required for the maintenance of pregnancy and has classically been considered virtually inactive due to associated very weak canonical estrogen signaling. However, estrogen exposure during pregnancy may have an effect on organs both within and outside the reproductive system, and compounds with binding affinity for estrogen receptors weaker than E3 have been found to impact reproductive organs and the brain. Here, we explore potential effects of E3 on fetal development using mouse as a model system. RESULTS: We administered E3 to pregnant mice, exposing the fetus to E3. Adult females exposed to E3 in utero (E3-mice) had increased fertility and superior pregnancy outcomes. Female and male E3-mice showed decreased anxiety and increased exploratory behavior. The expression levels and DNA methylation patterns of multiple genes in the uteri and brains of E3-mice were distinct from controls. E3 promoted complexing of estrogen receptors with several DNA/histone modifiers and their binding to target genes. E3 functions by driving epigenetic change, mediated through epigenetic modifier interactions with estrogen receptors rather than through canonical nuclear transcriptional activation. CONCLUSIONS: We identify an unexpected functional role for E3 in fetal reproductive system and brain. We further identify a novel mechanism of estrogen action, through recruitment of epigenetic modifiers to estrogen receptors and their target genes, which is not correlated with the traditional view of estrogen potency.

New Therapeutics in Endometriosis: A Review of Hormonal, Non-Hormonal, and Non-Coding RNA Treatments.

Endometriosis is defined as endometrial-like tissue outside the uterine cavity. It is a chronic inflammatory estrogen-dependent disease causing pain and infertility in about 10% of women of reproductive age. Treatment nowadays consists of medical and surgical therapies. Medical treatments are based on painkillers and hormonal treatments. To date, none of the medical treatments have been able to cure the disease and symptoms recur as soon as the medication is stopped. The development of new biomedical targets, aiming at the cellular and molecular mechanisms responsible for endometriosis, is needed. This article summarizes the most recent medications under investigation in endometriosis treatment with an emphasis on non-coding RNAs that are emerging as key players in several human diseases, including cancer and endometriosis.

Polycystic ovarian syndrome and infertility: overview and insights of the putative treatments.

Infertility concerns 15% of the couples. Management of female infertility requires a complete history of the patient followed by a physical, gynecological and endocrine examination. Infertility etiology will be investigated thanks to different tests including ovarian function and reserve assessment, search for uterine abnormalities and evaluation of tubal permeability. Polycystic ovarian syndrome (PCOS) is a predominant cause of infertility and a common gyne-endocrine disorder affecting 7 to 15% of women in reproductive age. Behavioral, medical and surgical treatments have been evaluated in order to improve the fertility of women with PCOS. Lifestyle modifications (stop smoking, physical exercise and weight loss when necessary) are of the utmost importance. Clomiphene citrate remains the first line of medical treatment of infertility in women with PCOS in absence of other male or female causes of infertility. Use of metformin solely for infertility is not recommended in absence of metabolic anomaly and new treatment as myoinositol is emerging. Surgical techniques aiming to enhance ovulation and pregnancy rate are an option when medical treatment failed. Ovarian drilling by laparoscopy or by transvaginal hydrolaparoscopy is taking a larger place in the treatment of infertility. In vitro maturation and fertilization remain the third-line of treatment in PCOS.

Choosing the right technique for deep endometriosis.

The surgical management of bowel endometriosis is a real challenge. In addition to the fact that only symptomatic patients should undergo surgery, no consensus has been approved in the literature. Among the surgical techniques, the surgeon has to choose between rectal shaving, disc excision, or segmental colorectal resection. All those procedures are associated with complications, but the risk of rectovaginal fistula is higher if a disc excision or segmental colorectal resection is performed. It is therefore of utmost importance to evaluate preoperatively the bowel infiltration by several imaging techniques to estimate the feasibility of a deep rectal shaving with possible incomplete removal of the endometriotic lesions or to discuss with the patient about the indication of a segmental bowel resection. Because of the risk of major preoperative and postoperative complications, proper patient counseling is mandatory.

Heterogeneity of estrogen receptor α and progesterone receptor distribution in lesions of deep infiltrating endometriosis of untreated women or during exposure to various hormonal treatments.

Deep infiltrating endometriosis (DIE) responds variably to hormonal therapy. Mutations in cancer driver genes have been identified in a fraction of the ectopic endometrial epithelial cells, suggesting a functional heterogeneity of these lesions. To evaluate the phenotype heterogeneity of cells in DIE, we measured the expression of estrogen receptor α (ERα) and of progesterone receptor (PR) in DIE of untreated women or under various treatments. We analyzed the luminal epithelial height (LEH), immunoreactive epithelial staining (IRS) and stromal staining intensity (SSI) of ERα and PR. We observed a high variability in the same gland, among distinct glands in the same sample and among distinct patients receiving the same treatment. LEH variability was primarily due to epithelial cells heterogeneity in a gland, secondarily to the glands randomly evaluated on the same section, and tertiary to the patient category. Variability in IRS and SSI scores was primarily the consequence of their heterogeneity in the same woman and to a lesser extent to variability among patients. LEH and SSI were not modified according to treatment. IRS for PR was lower in treated patients. This heterogeneity of ERα and PR distribution could explain why endocrine treatments are unable to cure this condition.