Impaired fertility in adenomyosis: a murine model reveals endometrial receptivity and progesterone resistance imbalances.

In brief: The impact of adenomyosis on reproductive health needs to be fully understood. By using a murine model, this study provides novel insights into the nuanced mechanisms associated with fertility challenges and offers a foundation for targeted interventions. Abstract: This study investigates the intricate relationship between adenomyosis and reproductive health using a murine model, offering novel insights into this prevalent gynecological disorder. Adenomyosis, characterized by the invasive growth of endometrial tissue into the myometrium, is believed to negatively impact fertility. However, the challenge lies in disentangling this influence, as adenomyosis often coexists with other gynecological diseases. A tamoxifen-induced mice model presents a significant advantage by enabling the specific study of adenomyosis, devoid of confounding influences of concurrent gynecological diseases such as endometriosis. Focusing exclusively on adenomyosis, our study aims to elucidate pathogenic mechanisms underlying fertility issues, focusing on estrous cyclicity, ovarian follicle development, and overall fertility. Our findings uncover disruptions in estrous cyclicity, characterized by an increased duration of time spent in the estrus phase in adenomyosis-induced mice. These disturbances are potentially linked to observed compromised folliculogenesis and the remarkable reduction in litter number and size in mice affected by adenomyosis. Moreover, this study unveils potential drivers of subfertility such as progesterone resistance and altered endometrial receptivity. Within the uteri of mice with adenomyosis, reduced expression of the progesterone receptor and a decreased expression of two implantation-related markers (HoxA10 and integrin ß3) were observed. This comprehensive examination sheds light on the nuanced complexities of adenomyosis-associated reproductive challenges, providing a foundation for targeted interventions in addressing fertility issues related to this disease.

[Prevention of infertility : recognizing and targeting numerous risk factors]. / Prévention de l'infertilité : reconnaître et cibler les nombreux facteurs de risque.

Follow-up consultations in gynaecology and general practice offer valuable opportunities to discuss fertility and the importance of a pre-conceptional assessment before attempting pregnancy. During these consultations, it is vital for healthcare professionals to provide patients with essential information about considerations before conceiving a child. Additionally, it is important to educate patients about basic hygiene practices that can impact both male and female fertility. The prevention of fertility disorders requires a holistic approach identifying and targeting numerous risk factors.

Les consultations de suivi en gynécologie et en médecine générale offrent des opportunités précieuses pour discuter de la fertilité et de l'importance d'une évaluation préconceptionnelle avant toute tentative de grossesse. Au cours de ces consultations, il est primordial pour les professionnels de santé de fournir aux patients des informations essentielles concernant les aspects à considérer avant de concevoir un enfant. De plus, il convient de sensibiliser les patients aux pratiques d'hygiène de base qui peuvent avoir un impact sur la fertilité masculine et féminine. La prévention des troubles de la fertilité nécessite une approche holistique identifiant et ciblant de nombreux facteurs de risque.

The mTOR Inhibitor Rapamycin Counteracts Follicle Activation Induced by Ovarian Cryopreservation in Murine Transplantation Models.

Background and Objectives: Ovarian tissue cryopreservation followed by autotransplantation (OTCTP) is currently the only fertility preservation option for prepubertal patients. Once in remission, the autotransplantation of frozen/thawed tissue is performed when patients want to conceive. A major issue of the procedure is follicular loss directly after grafting mainly due to follicle activation. To improve follicular survival during the OTCTP procedure, we inhibited the mTOR pathway involved in follicle activation using rapamycin, an mTOR inhibitor. Next, we compared two different in vivo models of transplantation: the recently described non-invasive heterotopic transplantation model between the skin layers of the ears, and the more conventional and invasive transplantation under the kidney capsule. Materials and Methods: To study the effects of adding rapamycin during cryopreservation, 4-week-old C57BL/6 mouse ovaries, either fresh, slow-frozen, or slow-frozen with rapamycin, were autotransplanted under the kidney capsule of mice and recovered three weeks later for immunohistochemical (IHC) analysis. To compare the ear with the kidney capsule transplantation model, fresh 4-week-old C57BL/6 mouse ovaries were autotransplanted to either site, followed by an injection of either LY294002, a PI3K inhibitor, vehicle control, or neither, and these were recovered three weeks later for IHC analysis. Results: Rapamycin counteracts cryopreservation-induced follicle proliferation, as well as AKT and mTOR pathway activation, in ovaries autotransplanted for three weeks under the kidney capsule of mice. Analyses of follicle proliferation, mTOR activation, and the effects of LY294002 treatment were similar in transplanted ovaries using either the ear or kidney capsule transplantation model. Conclusions: By adding rapamycin during the OTCTP procedure, we were able to transiently maintain primordial follicles in a quiescent state. This is a promising method for improving the longevity of the ovarian graft. Furthermore, both the ear and kidney capsule transplantation models were suitable for investigating follicle activation and proliferation and pharmacological strategies.

Impact of Assisted Reproduction Techniques on Adverse Maternal Outcomes and on the Rate of Hospitalization in Maternal Intensive Care.

Background and Objective: The aim of this retrospective cohort study is to evaluate the impact of assisted reproductive treatment (ART) on adverse maternal outcomes and the rate of hospitalization in maternal intensive care (MIC) in a tertiary university center in Liege, Belgium. Materials and Methods: This is a retrospective cohort study comparing two groups, 6557 patients who achieved pregnancy spontaneously and 330 patients who achieved pregnancy after ART, between January 2020 and December 2022. These patients were followed in the academic obstetrics department of Citadelle Hospital, Liège. The database of the ART center was compared with the database of the delivery unit to determine the cohort of patients who conceived after ART. Adverse maternal outcomes and MIC hospitalization rates were compared with between spontaneous pregnancies and ART groups. ART groups were also compared with each other. Results: The rate of hospitalization in maternal intensive care for patients who achieved pregnancy spontaneously was 12.1%, compared to 17.3% after ART. Comparing the rate of pre-eclampsia, 3.5% of spontaneous pregnancies were complicated by pre-eclampsia, while after ART, 10.9% of patients developed this complication during pregnancy. This rate was higher after IVF (12%) compared to intrauterine insemination and particularly after frozen embryo transfer (FET) in artificial cycle (17.9%). The birthweight of newborns after ART was also analyzed. A significant difference was obtained when comparing fresh embryo transfer with FET. Conclusions: Our study confirmed that FET in artificial cycle is a risk factor for pre-eclampsia and that fresh embryo transfer is associated with a higher rate of newborns with a lower percentile of birthweight. Our data showed that the rate of MIC hospitalization was significantly higher after ART but did not differ between groups.

Adenomyosis and Infertility: A Literature Review.

Background and Objectives: Adenomyosis (the presence of ectopic endometrial glands and stroma below the endometrial-myometrial junction) is a benign condition which is increasingly diagnosed in younger women suffering from infertility. The aim of this narrative review was to study the pathophysiology and prevalence of adenomyosis, the mechanisms causing infertility, treatment options, and reproductive outcomes in infertile women suffering from adenomyosis. Materials and Methods: A literature search for suitable articles published in the English language was performed using PubMed from January 1970 to July 2022. Results: The literature search retrieved 50 articles that met the purpose of this review and summarized the most recent findings regarding the accuracy of diagnostic methods, pathophysiology, and the prevalence of adenomyosis and optimal strategies for the treatment of infertile women with adenomyosis. Conclusions: Adenomyosis is a common gynecological disorder, affecting women of reproductive age. It negatively affects in vitro fertilization, pregnancy and the live birth rate, as well as increases the risk of miscarriage. With the advent of non-invasive diagnoses with MRI and TVUS, the role of adenomyosis in infertility has been better recognized. Overall, more randomized controlled trials (RCTs) are needed to provide strong data on the accuracy of diagnostic methods, the pathophysiology and the prevalence of adenomyosis, the fertility outcomes of patients and the optimal strategy for the treatment.

The Endometrial Microbiota: Challenges and Prospects.

Contrary to popular belief, we have known for many years that the endometrium is not a sterile environment and is considered to be a low-biomass milieu compared to the vagina. Numerous trials and studies have attempted to establish a valid sampling method and assess its physiological composition, but no consensus has been reached. Many factors, such as ethnicity, age and inflammation, can influence the microbiome. Moreover, it possesses a higher alpha-diversity and, therefore, contains more diverse bacteria than the vagina. For instance, Lactobacillus has been shown to be a predominant genus in the vaginal microbiome of healthy women. Consequently, even if a majority of scientists postulate that a predominance of Lactobacillus inside the uterus improves reproductive outcomes, vaginal contamination by these bacteria during sampling cannot be ruled out. Certain pathologies, such as chronic endometritis, have been identified as inflammation perpetrators that hinder the embryo implantation process. This pro-inflammatory climate created by dysbiosis of the endometrial microbiota could induce secondary inflammatory mediators via Toll-like receptors, creating an environment conducive to the development of endometriosis and even promoting carcinogenesis. However, studies to this day have focused on small populations. In addition, there is no clearly defined healthy uterine composition yet. At most, only a few taxa have been identified as pathogenic. As sampling and analysis methods become increasingly precise, we can expect the endometrial microbiota to be incorporated into future diagnostic tools and treatments for women's health.

[Villar's nodule]. / Nodule de Villar.

Umbilical endometriosis is a rare manifestation, most often isolated, of endometriosis, accounting for 0,5-1 % of all cases. It can be primary or secondary following surgery. It usually presents as a solid, skin-colored, red or purple-black nodule, frequently associated with pain and/or perimenstrual bleeding. Because it has a potential for malignant transformation, the gold standard of treatment is surgical removal.

L'endométriose ombilicale, ou nodule de Villar, est une manifestation rare et le plus souvent isolée d'endométriose, survenant dans 0,5 à 1 % des cas. Elle peut être primaire ou secondaire à une intervention chirurgicale. Elle se manifeste habituellement par un nodule ferme, de couleur chair, rouge ou violet-noir, fréquemment associé à des douleurs et/ou des saignements péri-menstruels. Il existe un risque potentiel de transformation maligne, raison pour laquelle le traitement de première intention est l'exérèse chirurgicale.

[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.

[Management of tubal ectopic pregnancies with methotrexate : is it an effective treatment ?] / La prise en charge des grossesses extra-utérines tubaires par méthotrexate : un traitement efficace ?

Ectopic pregnancy is a gynecological emergency. The hCG level, the clinical presentation and the ultrasound remain the key steps for the diagnosis. The criteria tend to be more and more codified to decide on the optimal treatment, however, there is no consensus. The aim of this study was to evaluate the impact of applying a mathematical formula to predict the failure rate of metho-trexate for tubal ectopic pregnancy. A retrospective, monocentric study was conducted on a cohort of 193 patients for whom the formula could be calculated. Regarding our professional practice, the success rate of first-line metho-trexate is 93 %. It would increase to 96 % if the formula had been applied. The use of the formula would also reduce the rate of first-line surgery by 12 %.

La grossesse extra-utérine est une urgence gynécologique. Le taux d'hCG, la clinique et l'échographie restent les examens clé pour le diagnostic. Les critères tendent à être de plus en plus codifiés pour décider du traitement optimal. Cependant, il n'existe aucun consensus. Le but de cette étude était d'évaluer l'impact de l'application d'une formule mathématique permettant de prédire le taux d'échec du méthotrexate pour une grossesse extra-utérine tubaire. Une étude rétrospective et monocentrique a été menée sur une cohorte de 193 patientes pour lesquelles la formule a pu être calculée. Concernant notre pratique professionnelle, le taux de réussite du méthotrexate en 1ère intention est de 93 %. Il passerait à 96 % si la formule avait été appliquée. L'emploi de la formule permettrait également de diminuer de 12 % le taux de chirurgie réalisée en première intention.

[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.

Evaluation of an alternative heterotopic transplantation model for ovarian tissue to test pharmaceuticals improvements for fertility restoration.

BACKGROUND: Ovarian tissue cryopreservation and transplantation (OTCTP) is currently the main option available to preserve fertility in prepubertal patients undergoing aggressive cancer therapy treatments. However, a major limitation of OTCTP is follicle loss after transplantation. The mouse is a model of choice for studying ovarian function and follicle development after ovarian tissue grafting in vivo. In these mouse models, ovarian tissue or ovaries can be transplanted to different sites. Our aim was to evaluate a new alternative to heterotopic transplantation models that could be useful to test pharmaceutical improvement for ovarian grafts after OTCTP. METHODS: Slow frozen murine whole ovaries were transplanted into the mouse ears (between the external ear skin layer and the cartilage). Ovarian transplants were recovered after 3, 14 or 21 days. Grafts were analyzed by immunohistochemistry and follicle density analyses were performed. RESULTS: An increase of ovarian vascularization (CD31 and Dextran-FITC positive staining), as well as cellular proliferation (Ki67 staining) were observed 3 weeks after transplantation in comparison to 3 days. Fibrosis density, evaluated after Van Gieson staining, decreased 3 weeks after transplantation. Furthermore, transplantation of cryopreserved ovaries into ovariectomized mice favored follicle activation compared to transplantation into non-ovariectomized mice. CONCLUSION: The present study indicates that surgical tissue insertion in the highly vascularized murine ear is an effective model for ovarian grafting. This model could be helpful in research to test pharmaceutical strategies to improve the function and survival of cryopreserved and transplanted ovarian tissue.

Impact on ovarian reserve and fertility using carbon dioxide laser for endometriosis treatment: a systematic review.

BackgroundThe application of carbon dioxide (CO2) laser for laparoscopic gynecologic surgery was introduced in 1979 and spread after improving instrumentation, due to the versatility of the CO2 laser technology and the parallel increase of laparoscopic use. In a gynecologic setting, laser laparoscopy has been demonstrated to be effective in treating infertility and pain associated with mild to severe endometriosis.Aim and methods: This document aims at conducting a systematic review to provide a comprehensive literature overview regarding the rationale, indications, safety, and efficacy of CO2 laser treatment of endometriosis and related outcomes on ovarian reserve and fertility.ResultsCO2 laser seems to lead to lower heat damage in the ovarian tissue than bipolar energy during endometriomas treatment. Moreover, several reports have pointed out that laser vaporization allows to selectively destroy the endometrioma wall's internal surface, preserving the pericystic fibrotic capsule or the adjacent healthy ovarian cortex. Despite this, robust data we have so far indicates that the most effective laparoscopic approach for managing endometriomas is the traditional excisional technique providing better postoperative outcomes than drainage and electrocoagulation, and laser treatment. Data about fertility after treatment of deep infiltrating endometriosis (DIE) using dioxide laser are emerging but very poor.ConclusionsCurrent scientific evidence in this field is inconclusive, and the debate about the safety and efficacy of the CO2 laser on fertility outcomes is still ongoing. Further randomized case-control studies are mandatory to attain more consistent evidence.

First-line noninvasive management of cytomegalovirus primary infection in pregnancy.

OBJECTIVES: To introduce a first-line noninvasive antenatal management of maternal cytomegalovirus (CMV) primary infection based on ultrasound (US) and magnetic resonance imaging (MRI). Amniocentesis (AC) is used as a second-line tool in cases of abnormalities compatible with fetal CMV infection on US and/or MRI screening. METHODS: Between January 2011 and October 2018, pregnant women referred with a CMV primary infection on antibody screening were followed up by monthly US scans and a brain MRI at approximately 32 weeks. In cases with US and/or MRI abnormalities compatible with congenital CMV infection, AC was performed to confirm the diagnosis. RESULTS: Ninety pregnant women with a primary CMV infection were included (89 singleton and one twin pregnancy). The first-line screening by US and/or MRI was normal for 72 of 91 fetuses (79%). At birth, 19 of these 72 neonates (26%) had a positive urine sample for CMV but were asymptomatic. US and/or MRI abnormalities were identified in 19 fetuses (21%). AC confirmed a fetal CMV infection in 16 fetuses (84%); 12 pregnancies were terminated, and four were continued, with three symptomatic neonates at birth and one poor neurodevelopmental outcome at postnatal follow-up. CONCLUSIONS: First-line noninvasive management of maternal CMV primary infection based on serial US scans and brain MRI can be offered to identify fetuses with severe symptomatic congenital CMV infection and reduce the number of ACs without compromising the fetal outcome.

Human Chorionic Gonadotropin and Early Embryogenesis: Review.

Human chorionic gonadotropin (hCG) has four major isoforms: classical hCG, hyperglycosylated hCG, free ß subunit, and sulphated hCG. Classical hCG is the first molecule synthesized by the embryo. Its RNA is transcribed as early as the eight-cell stage and the blastocyst produces the protein before its implantation. This review synthetizes everything currently known on this multi-effect hormone: hCG levels, angiogenetic activity, immunological actions, and effects on miscarriages and thyroid function.

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.

Pseudotumoral Endometriotic Nodule.

STUDY OBJECTIVE: To demonstrate a rare case of a pediculated endometriotic nodule that was initially diagnosed as a solid adnexal mass. DESIGN: We present a stepwise narrated demonstration of our laparoscopic technique. SETTING: We present a case report of a patient aged 44 years, gravida 2 para 2, who was diagnosed with a solid (adnexal) mass during a gynecologic examination. She presented symptoms of dyspareunia. During a bimanual examination, 2 fixed nodules were palpated in both the uterosacral ligaments, and a mobile solid mass of 5 cm could be palpated on the right adnex. A transvaginal ultrasound showed a solid (adnexal) mass of 50 mm in diameter. The tumor marker cancer antigen 125 was normal, and after application of the International Ovarian Tumor Analysis score, the risk of malignancy was up to 39%. A complementary magnetic resonance image showed a heterogeneous solid mass of 47 × 47 × 29 mm with a differential diagnosis of a pediculated fibroma in (myxoid) degeneration vs an adnexal solid mass. A laparoscopic unilateral adnexectomy was scheduled, and the patient was informed about the risk of malignancy. The laparoscopy revealed bilateral normal adnexa, the presence of a solid pediculated mass originating from the right uterosacral ligament and 2 endometriotic nodules originating from the left and right uterosacral ligaments. The rectovaginal space was dissected, and a third deep infiltrating endometriotic nodule was revealed. The operation proceeded by the sectioning of the left uterosacral ligament below the endometriotic nodule. The posterior vaginal wall was separated from the endometriotic nodule, and after further dissection of the rectovaginal space, we arrived in a disease-free area. After opening of the right medial division of the pararectal space, the right hypogastric nerve was dissected and preserved. The solid mass was separated from the uterus, the right uterosacral ligament was excised at a distance from the nodule, and the pediculated mass was removed intact en block with the right ligament. The patient was discharged 24 hours after surgery. The postoperative period was uneventful. The definitive histology report confirmed the presence of endometriotic nodules and a solid tumor classified as a pseudotumoral endometriotic mass. This was justified by the presence of conjunctival vascular stroma including multiple endometriotic foci, the presence of cytogenic stroma of variable abundance including glands lined with a columnar epithelium, and, most important, the fact that the epithelium had no cytologic atypias. INTERVENTIONS: Laparoscopic excision of the pseudotumoral endometriotic nodule en block with the right and left uterosacral ligaments. CONCLUSION: Endometriosis is a complex multifactorial pathology in which several factors are involved: genetics, environmental factors, immunologic reactions, hormonal effects, and anatomic anomalies. All these factors may contribute to the creation of an inflammatory response related to immune cells, adhesion molecules, extracellular matrix metalloproteinase, and proinflammatory cytokines enhancing the formation of fibrotic tissue [1,2]. These changes may sometimes have an unusual presentation, as we are showing in this case report of a pseudotumoral endometriotic mass. This rare case should be included in the differential diagnosis of solid tumors before surgery for symptomatic patients and those who have a medical history of endometriosis.

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.

Absence of correlation between follicular fluid volume and follicular granulocyte colony-stimulating factor, a predictor of embryo implantation and successful delivery.

Follicular granulocyte colony-stimulating factor (G-CSF) is a documented marker of embryo implantation potential. The primary objective was to determine whether follicular G-CSF levels correlate with follicular fluid volume. The secondary objectives were to assess whether follicular G-CSF is associated with oocyte maturity at the time of harvest and with delivery rate after fresh or frozen embryo transfer. Thirty-two patients undergoing intracytoplasmic sperm injection (ICSI) cycles were recruited (Centre de Procréation Médicalement Assistée (CPMA), University of Liège, Belgium). A total of 211 follicular fluid (FF) samples were individually collected at the time of oocyte harvest. FF volume was recorded, and G-CSF concentration was assessed by ELISA. The embryos were individually cultured in vitro. Their implantation and live birth rates were recorded after fresh and frozen embryo transfers. The follicular fluid volume did not correlate with the follicular G-CSF concentration. There were no differences in follicular G-CSF levels between mature and immature oocytes. The probability of successful implantation and delivery was increased for embryos with FF containing a high G-CSF concentration. There was a trend toward lower follicular G-CSF levels in cases of miscarriage. Therefore, follicular fluid volume cannot be a substitute for follicular G-CSF as a marker of embryo implantation ability.

A paracrine interaction between granulosa cells and leukocytes in the preovulatory follicle causes the increase in follicular G-CSF levels.

OBJECTIVE: Follicular granulocyte colony-stimulating factor (G-CSF) is a new biomarker of oocyte quality and embryo implantation in in vitro fertilization (IVF) cycles. Its role in reproduction is poorly understood. Our study aimed to investigate the mechanisms and cells responsible for G-CSF production in the preovulatory follicle. DESIGN: Laboratory research study. SETTING: Single-center study. INTERVENTIONS: Granulosa cells and leukocytes were isolated from the follicular fluids (FF) or the blood of women undergoing IVF and from the blood of a control group of women with spontaneous ovulatory cycles to perform cocultures. MAIN OUTCOME MEASURE: G-CSF-secreted protein was quantified in the conditioned media of cocultures. RESULTS: G-CSF secretion was considerably increased in cocultures of granulosa cells and leukocytes. This effect was maximal when leukocytes were isolated from the blood of women in the late follicular phase of the menstrual cycle or from the FF of women undergoing IVF. The leukocyte population isolated from the FF samples of women undergoing IVF had a higher proportion of granulocytes than that isolated from the corresponding blood samples. Leukocytes induced the synthesis and secretion of G-CSF by granulosa cells. Among a range of other FF cytokines/chemokines, only growth-regulated oncogene alpha (GROα) was also increased. CONCLUSION: The notable rise in G-CSF at the time of ovulation coincides with the accumulation of follicular granulocytes, which stimulate G-CSF production by granulosa cells via paracrine interactions. High follicular G-CSF concentrations may occur in follicles with optimal granulosa-leukocyte interactions, which could explain the increased implantation rate of embryos arising from these follicles.

Importance of n-3 PUFA consumption during pregnancy: perception discrepancies between pregnant women and gynaecologists-obstetricians in Belgium.

OBJECTIVE: n-3 PUFA during pregnancy have been subject to intense research interest, but also much controversy, creating a situation of confusion among patients and health-care providers. The present study was carried out to explore knowledge, attitude and practices regarding n-3 PUFA in two independent populations of pregnant women and gynaecologists-obstetricians in Belgium and to assess the relationship between the pregnant women's attributes and their n-3 PUFA status measured by the omega-3 index. DESIGN: Cross-sectional study. Knowledge, attitude and practices were collected by self-administered questionnaires while laboratory data were available for each pregnant woman. SETTING: During the first antenatal hospital appointment (for the pregnant women) and by email (for the gynaecologists-obstetricians).ParticipantsWomen in early pregnancy (n 122) and gynaecologists-obstetricians (n 67). RESULTS: Marked discrepancies in perception were evidenced between the pregnant women and health-care providers. While 82 % of the women attached high importance to n-3 PUFA during pregnancy, only a third of the gynaecologists-obstetricians did. About 35 % of the women declared paying particular attention to their consumption of n-3 PUFA. After adjusting for sociodemographic characteristics, these positive dietary practices were significantly associated with higher omega-3 index (P=0·04). Overall, 43·3 % of professionals did not provide any information about n-3 PUFA to their pregnant patients and 46·3 % did not take any preventive actions. CONCLUSIONS: Evidence-based guidelines, refreshment training and communication tools are needed to improve awareness and clinical practices among caregivers regarding n-3 PUFA to benefit both mothers and their children.