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Objective: To study the impact of a CT serology on intrauterine insemination (IUI) cumulative live-birth rate (cLBR) in women with documented bilateral tubal patency., Design: Cohort study SUBJECTS: Infertile women with documented bilateral tubal patency and medical indication of IUI matched on the following criteria: woman's age, number of cycles completed and number of motile sperm inseminated (NMSI)., Exposure: This retrospective, observational and monocentric cohort study compared women with positive CT serology matched 1:1 to control women with negative CT serology., Main Outcome Measures: Cumulative LBR, rates of clinical pregnancy, spontaneous abortion, biochemical pregnancy., Results: A total of 71 women in the CT positive group were matched to 71 women in the negative CT group, leading to compare 136 cycles per group. No statistically significant difference was observed between groups regarding the demographic and medical characteristics of couples. Cumulative LBR per woman was similar in both groups with 32.4% (n = 23) in the negative serology group Vs 25.4% (n = 18) in the positive CT group (NS). The rates of clinical pregnancy, spontaneous abortion, biochemical pregnancy were comparable between the two groups., Conclusion: In a population of infertile women with patent tubes, our study suggests that the serological status for CT has no impact on the IIU cLBR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author Blandine Courbiere is an Editorial Board Member for Journal of Gynecology Obstetrics and Human Reproduction and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To explore the regulatory role of soluble CD146 (sCD146) and its interaction with galectin-1 (Gal1) in placenta-mediated complications of pregnancy., Design: Prospective pilot and experimental studies., Setting: University-affiliated hospital and academic research laboratory., Patient(s): One hundred fifteen women divided into three groups: 30 healthy, nonpregnant women, 50 women with normal pregnancies, and 35 with placenta-mediated pregnancy complications., Intervention(s): Wound-healing experiments were conducted to study trophoblast migration., Main Outcome Measure(s): Quantification of sCD146 and Gal1 by enzyme-linked immunosorbent assay. Analysis of trophoblast migration by wound closure., Result(s): Concomitant detection of sCD146 and Gal1 showed lower sCD146 and higher Gal1 concentrations in women with normal pregnancies compared with nonpregnant women. In addition, follow-up of these women revealed a decrease in sCD146 associated with an increase in Gal1 throughout pregnancy. In contrast, in women with preeclampsia, we found significantly higher sCD146 concentrations compared with women with normal pregnancies and no modification of Gal1. We emphasize the opposing effects of sCD146 and Gal, since, unlike Gal1, sCD146 inhibits trophoblast migration. Moreover, the migratory effect of Gal1 was abrogated with the use of an anti-CD146 blocking antibody or the use of small interfering RNA to silence VEGFR2 expression. This suggests that trophoblast migration is mediated though the interaction of Gal1 with CD146, further activating the VEGFR2 signaling pathway. Significantly, sCD146 blocked the migratory effects of Gal1 on trophoblasts and inhibited its secretion, suggesting that sCD146 acts as a ligand trap., Conclusion(s): Soluble CD146 could be proposed as a biomarker in preeclampsia and a potential therapeutic target., Clinical Trial Registration Number: NCT 01736826., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

CD146 is an adhesion molecule essentially located in the vascular system, which has been described to play an important role in angiogenesis. A soluble form of CD146, called sCD146, is detected in the bloodstream and is known as an angiogenic factor. During placental development, CD146 is selectively expressed in extravillous trophoblasts. A growing body of evidence shows that CD146 and, in particular, sCD146, regulate extravillous trophoblasts migration and invasion both in vitro and in vivo . Hereby, we review expression and functions of CD146/sCD146 in the obstetrical field, mainly in pregnancy and in embryo implantation. We emphasized the relevance of quantifying sCD146 in the plasma of pregnant women or in embryo supernatant in the case of in vitro fertilization (IVF) to predict pathological pregnancy such as preeclampsia or implantation defect. This review will also shed light on some major results that led us to define CD146/sCD146 as a biomarker of placental development and paves the way toward identification of new therapeutic targets during implantation and pregnancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bouvier, Kaspi, Joshkon, Paulmyer-Lacroix, Piercecchi-Marti, Sharma, Leroyer, Bertaud, Gris, Dignat-George, Blot-Chabaud and Bardin.)

Background: The purpose of this retrospective observational study was to identify prognostic factors that lead to a live birth (LB) in couples with unexplained infertility in order to define the best assisted-reproductive technique (ART) strategy., Methods: Prognostic factors of couples with unexplained infertility managed initially with gonadotropin intrauterine inseminations (IUI) at a single university fertility center were analyzed. Infertility was not considered "unexplained" in case of mild male infertility and suspicion of diminished ovarian reserve (FSH>10 IU/L). ART management consisted to start with IUI cycles and then, if failure, to propose in vitro fertilization (IVF). Couples were compared according to the results of IUI cycles in terms of LB., Results: Between January 2011 and July 2015, 133 couples with unexplained infertility were included (320 IUI cycles). The average age of women was 31.6±4.6 years and the average number of IUI per couple was 2.4±1.2. The IUI live birth rate (LBR) was 37.6%, with an average of 2 cycles to obtain a pregnancy. For 63 couples, no pregnancy occurred after IUI cycles. The prognostic factors of the two groups "LB after IUI" vs. "no LB after IUI" were not statistically different. The remaining 20 couples had a spontaneous pregnancy with a LB. Cumulative LBR, including spontaneous and ART pregnancies, was 65.7%. Of the 63 couples with no LB after IUI, 33.3% dropped-out from infertility treatments before starting IVF., Conclusions: To avoid couple's drop-out, we advise to start infertility treatment for unexplained infertility with two IUI before undergoing IVF if IUI failure.

Although progress was made in in vitro fertilization (IVF) techniques, the majority of embryos transferred fail to implant. Morphology embryo scoring is the standard procedure for most of IVF centres for choosing the best embryo, but remains limited since even the embryos classified as "top quality" may not implant. As it has been shown that i) CD146 is involved in embryo implantation and ii) membrane form is shed to generate soluble CD146 (sCD146), we propose that sCD146 in embryo supernatants may constitute a new biomarker of embryo selection. Immunocytochemical staining showed expression of CD146 in early embryo stages and sCD146 was detected by ELISA and Western-blot in embryo supernatants from D2. We retrospectively studied 126 couples who underwent IVF attempt. The embryo culture medium from each transferred embryo (n = 222) was collected for measurement of sCD146 by ELISA. Significantly higher sCD146 concentrations were present in embryo supernatants that did not implant (n = 185) as compared to those that successfully implanted (n = 37) (1310 +/- 1152 pg.mL-1 vs. 845+/- 1173 pg.mL-1, p = 0.024). Sensitivity analysis performed on single embryo transfers (n = 71) confirmed this association (p = 0.0054). The computed ROC curve established that the optimal sCD146 concentration for embryo implantation is under 1164 pg.mL-1 (sensitivity: 76%, specificity: 48%, PPV: 25% and NPV: 92%). Over this sCD146 threshold, the implantation rate was significantly lower (9% with sCD146 levels >1164 pg.ml-1 vs. 22% with sCD146 levels ≤ 1164 pg.mL-1, p = 0.01). Among the embryos preselected by morphologic scoring, sCD146 determination could allow a better selection of the embryo(s), thus improving the success of elective single embryo transfer. This study establishes the proof of concept for the use of sCD146 as a biomarker for IVF by excluding the embryo with the highest sCD146 level. A multicentre prospective study will now be necessary to further establish its use in clinical practice.

Objective: To identify the prognostic factors for pregnancy after intrauterine insemination with the husband's sperm (IUI-H)., Design: Retrospective study., Setting: A single university medical center., Patient(s): 851 couples, for 2,019 IUI-H cycles., Intervention(s): After controlled ovarian stimulation, IUI-H performed 36 hours after ovulation triggering or 24 hours after a spontaneous luteinizing hormone (LH) surge., Main Outcome Measure(s): Clinical pregnancy rate per cycle (PR) and delivery rate per cycle (DR)., Result(s): The overall PR was 14.8% and DR 10.8%. Higher PR and DR were observed for patients presenting with ovulation disorders (particularly polycystic ovary syndrome) or with male infertility. Secondary infertility in the woman appeared to be a positive prognostic factor as did a basal follicle-stimulating hormone (FSH) level ≤ 7 IU/L and ovulation triggering over spontaneous LH rise. The other parameters influencing the results were the women's age, the number of mature follicles obtained (≥ 2), the endometrial thickness (10-11 mm), and the number of progressive motile spermatozoa inseminated (>1 million)., Conclusion(s): In women aged ≤ 38 years, IUI-H should be considered as an option, particularly in cases of female infertility from ovulation disorders, in cases of a normal ovarian reserve, in cases of secondary infertility, or when ≥ 1 million progressive sperm are inseminated. Bifollicular stimulation is required. In other cases, in vitro fertilization should be discussed as the first-line treatment., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Implantation failure could be related to antiphospholipid antibodies (aPL). We retrospectively analyzed the usefulness of aPL determination in women undergoing IVF. Conventional aPL of the antiphospholipid syndrome, lupus anticoagulant (LA), anticardiolipin antibodies (aCL), anti-β2glycoprotein I (a β2GPI) antibodies, and IgG and IgM isotypes as well as IgA isotype were analyzed in women presenting with at least two implantation failures after in vitro fertilization (IVF). In a population of 40 IVF patients, a total prevalence of 20% (8/40) of aPL was found, significantly different from that of the control population (100 healthy blood donors, P < 0.0005). Among the panels of aPL tested, a β2GPI IgA antibodies were the most prevalent (62.5% 5/8), significantly higher in IVF patients (12.5%, 5/40) than in controls (1%, 1/100) (P = 0.01). No difference according to the numbers of IVF attempts and success of embryo implantation was found between aPL positive and negative IVF patients. In contrast, no accomplished pregnancy with full-term live birth was observed in aPL positive IVF patients. Altogether our data led us to propose aPL assessment, in particular a β2GPI IgA antibodies, in support of IVF treated women. In a perspective way, an early aPL detection could be the basis for defining novel therapeutic strategy.

We compared the abilities of two commonly used semen preparation techniques to decrease the amount of benzo(a)pyrene-diol-epoxide (BPDE)-DNA adducts in the spermatozoa of ten smokers. Semen processing by swim-up or discontinuous gradient centrifugation recovered spermatozoa showing an equally significantly lower amount of BPDE-DNA adducts than in unprepared spermatozoa from neat semen., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Epicardial white adipose tissue (eWAT) is in close contact with coronary vessels and therefore could alter coronary homeostasis. Adrenomedullin (AM) is a potent vasodilatator and antioxidative peptide which has been shown to play a cytoprotective role in experimental models of acute myocardial infarction. We studied, using immunohistochemistry and qRT-PCR, the expression of AM and its receptors calcitonin receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP)2 and -3 in paired biopsies of subcutaneous WAT (sWAT) and eWAT obtained from patients with coronary artery disease (CAD) or without CAD (NCAD). In eWAT obtained from NCAD or CAD patients, immunoreactivity for AM, CRLR, and RAMP2 and -3 was detected in blood vessel walls and isolated stromal cells close to adipocytes. Some of the AM positive stromal cells colocalized CD68 immunoreactivity. eWAT from CAD patients showed increased AM immunoreactivity and AM gene expression. CRLR mRNA levels were comparable in sWAT of both groups and decreased by 40-50% in eWAT, irrespectively of the coronary status. RAMP2 mRNA concentrations did not change while RAMP3 mRNA levels increased in sWAT from CAD patients. There was a positive linear relationship between eWAT 11beta-hydroxysteroid dehydrogenase type 1 mRNA (11beta-HSD-1, the enzyme that converts inactive to active glucocorticoids) and AM mRNA. In conclusion, we demonstrate that AM and its receptors are expressed in eWAT. Our data suggest that eWAT AM, which could originate from macrophages, is related to 11beta-HSD-1 expression. AM synthesis, which is increased in eWAT during chronic CAD in humans, can play a cardioprotective role.

The aim of this study was to describe the association between various percentages of macronuclear spermatozoa (MNSs), sperm chromosomal abnormalities, and reproductive failure in 4 patients. One patient had a familial history of perinatal deaths. Patients were selected according to the coexistence of normal-sized spermatozoa and MNSs (19%, 22%, 29.5%, and 49.7%). Fluorescent in situ hybridization (FISH) on spermatozoa and semiautomated analysis of nuclear surface were assessed. All patients were characterized by an oligoasthenozoospermia. Three patients had a prevalence of irregular MNSs and prevalence of nondisjunction at the first meiotic division. One patient had a prevalence of regular MNSs and a prevalence of nondisjunction at the second meiotic division. FISH also showed a high rate of polyploidy and various rates of aneuploid sperm. The percentage of sperm with abnormal chromosome complements (25.6%, 43.6%, 51.4%, 71.7% with 3-color FISH) was higher than the percentage of MNSs. A population of apparently normal-sized spermatozoa that could be used for intracytoplasmic sperm injection (ICSI) was aneuploid. Sperm nuclear surface analysis revealed either a shift toward elevated values or distinguished 2 sperm subpopulations: normal and macronuclear. Patients underwent 7 ICSI cycles. The fertilization rate was low for 3 patients (50%, 40%, 50%) and normal for 1 patient (83.3%). Pregnancy rate per transfer was low (14.3%). The present study shows that the macronuclear phenotype can manifest a variety of clinical aspects. It is also shown that mild rates of MNSs impair fertility and constitute a risk of chromosomal abnormality for the embryos and a risk of perinatal death. We suggest conducting FISH on spermatozoa and genetic counseling for a couple when the percentage of MNSs reaches 20% in at least 1 spermiogram.

Objective: Glucocorticoids may be a pathophysiological mediator for the development of visceral obesity. In obese patients, adipose tissue reactivation of cortisone to cortisol is enhanced. In addition, changes in glucocorticoid receptor (GR) could also be important, either at the central nervous system level, by modulating the negative glucocorticoid feedback, or at a peripheral level, by regulating adipose tissue activity., Research Methods and Procedures: Using quantitative reverse transcriptase-polymerase chain reaction, we studied the expression of the GR mRNA isoforms (active, GRalpha; inactive, GRbeta) in circulating mononuclear leukocytes (in which GR shares the same regulation with central nervous system GR) obtained from normal weight women (n = 65) and patients with gluteofemoral (n = 26) or visceral (n = 39) obesity. Using in situ hybridization, we measured GRalpha mRNA levels in adipose tissue from control (n = 10) or obese (n = 15) patients., Results: The mean alpha/beta ratio was decreased in mononuclear leukocytes from obese patients (2.6, 9.2, and 32.1, respectively). GRalpha mRNA levels were significantly decreased in subcutaneous abdominal adipose tissue obtained from obese patients compared with nonobese ones, suggesting the existence of a downregulation of GR gene expression. This phenomenon was not found in visceral adipose tissue., Discussion: This suggests that, in obese patients, the relative insensitivity to the negative glucocorticoid feedback is, at least in part, subsequent to a dysregulation of the GRalpha/GRbeta ratio and that visceral, but not subcutaneous, adipose tissue retains a full capacity to respond to increased local generation of cortisol.

Glucocorticoids are implicated as a pathophysiological mediator of obesity and its accompanying metabolic and cardiovascular complications. Obese patients exhibit normal circulating cortisol levels, related to increased glucocorticoid production and degradation. However, it has been demonstrated that local production of active cortisol from inactive cortisone driven by 11 beta-hydroxysteroid dehydrogenase type 1 is exaggerated in adipose tissue of obese subjects. Such local hypercortisolism may be responsible for increased adipocyte differentiation and enhanced secretion of free fatty acids and other substances involved in the metabolic and cardiovascular complications observed in obesity.

Objective: To evaluate obstetric outcome of pregnancies and pediatric follow-up of children born after ICSI procedure., Material and Method: Prospective study from october 1994 to September 1998 in medical assisted procreations center in La Conception hospital in Marseilles. Three hundred forty-two couples undergoing ICSI procedures., Interventions: analysis of pregnancy rates, prematurity rates, obstetric outcome and frequency of congenital malformations., Results: One hundred seventy-eight pregnancies have been obtained with 111 children. Multiple pregnancy rate arise 29.7%. The average term at birth in the singleton pregnancies (38.7 weeks) is higher than in the twins (35.7 weeks). The prematurity rate of delivery before 35 weeks of gestation is about 9.6%. Seven of 111 neonates was born with a congenital malformation, no cardiovascular one. One of boys presents a bilateral cryptorchidism with severe bilateral hypotrophy., Conclusions: Our results are similar with those of others teams. Congenital malformation rates is near rates reported in others studies. However, no bilateral cryptorchidism with bilateral severe hypotrophy has been yet reported in literature.

We analyzed retrospectively 936 intrauterine insemination (IUI) cycles with husband's sperm (384 couples). Superovulation and induction monitoring occurred in the majority of cases; IUI was timed 36-40 h after ovulatory hCG. The overall pregnancy rate per cycle (PR/C) was 11.4% (107/936). Data analysis demonstrated that PR/C decreased with infertility duration, woman's age (especially after 38 years old) and number of attempts (significantly after the 4 th cycle). Superovulation (in particular by antiestrogens) and induction monitoring seemed to provide an increase in cycle pregnancy rate. Highest PR/C were observed in dysovulation and male infertility groups. In cases of sperm defects, our data showed that 2 parameters had a significant influence on pregnancy outcome: the number of motile progressive inseminated spermatozoa (> 300,000) and the spermatozoa survival rate after 24 h (> 50%). As a conclusion, intrauterine insemination can be proposed as a satisfying treatment of infertility, if precise protocol is followed and its indications well-defined.

In vitro, estrogens stimulate corticotropin-releasing factor (CRF) gene transcription. In ovariectomized (OVX) rats, estrogens have a negative effect on CRF mRNA levels in the hypothalamic paraventricular nucleus. This suggests that the stimulatory influence of estrogens found in vitro may be masked in vivo by an inhibitory effect mediated through neural and/or humoral factors. Glucocorticoids may be involved in this phenomenon since estrogens increase circulating corticosterone levels in OVX rats. We studied the effect of 7-day 17 beta-estradiol (E2) treatment on CRF gene expression in the paraventricular nucleus of 2-week OVX mature rats after sham operation or adrenalectomy (ADX) with or without corticosterone replacement. In sham ADX animals, E2 administration increased plasma corticosterone concentrations, did not change the binding capacity or the affinity of circulating corticosteroid binding globulin, and decreased hypothalamic CRF gene expression. Following ADX, CRF mRNA levels increased and were normalized by corticosterone treatment. Estrogens induced a significant build up in CRF mRNA concentrations in both ADX or ADX corticosterone-replaced animals. Our data demonstrate that the positive effect of estrogens on CRF gene expression found in vitro or in vivo after ADX is antagonized, in vivo when the adrenal glands are intact, by a negative influence. They strongly suggest that the increased circulating corticosterone levels induced by E2 administration mediate the inhibitory effect of estrogens on CRF mRNA levels. These observations may explain the gender related differences in the basal and stress-induced hypothalamo-pituitary-adrenal activity.

It is known that estrogens modulate the hypothalamopituitary-adrenal (HPA) axis both under resting conditions and during exposure to stress. Nevertheless, the site of action of estrogens is not still fully elucidated. We sought to determine if estrogens could act on the major hypothalamic ACTH secretagogue: corticotropin-releasing factor (CRF). Mature rats were ovariectomized (OVX) and 2 weeks later implanted with silastic capsules containing 17β-estradiol (E(2)). Animals were sacrificed 7 days later. CRF mRNA in the hypothalamic paraventricular nucleus (PVN) and proopiomelanocortin (POMC) mRNA in the anterior pituitary were measured byin situ hybridization. CRF content in the median eminence was measured by semiquantitative immunocytochemistry. E(2) treatment induced a significant decrease of CRF mRNA levels in the PVN (3.70±0.14vs 4.79±0.15 copies of probe×10(-3)/μm(3) of tissue in OVX rats,P<0.05), an accumulation of immunoreactive CRF in the zona externa of the median eminence (207±36vs 100±15% in OVX rats,P<0.05), and a decrease of POMC mRNA levels in the anterior pituitary (4.6±0.6vs 6.9±0.6 copies of probe ×10(-2)/μm(3) of tissue in OVX rats,P<0.05). These results demonstrate that estrogens have a negative effect on CRF gene expression and secretion and on POMC gene expression. Whether estrogens modulate directly the CRF-synthesizing cells or act through an increase of the glucocorticoid negative feedback remains to be determined.

ACTH secretion is mainly controlled by two hypothalamic neurohormones: corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). Both peptides are synthesized in the hypothalamic paraventricular nucleus (PVN) (in parvo-cellular neurons for CRH and in magnocellular neurons for most AVP). Under basal conditions, some CRH neurons coexpress AVP (CRH+/AVP+ neurons). This colocalisation represents a form of functional plasticity since the number of CRH+/AVP+ neurons increases after acute or repeated stress exposure. Experiments in sheep and rat (studies on the secretion of both peptides in hypophysial portal blood, effects of anti-CRH and anti-AVP immunisation upon ACTH secretion) indicate that stress-induced ACTH stimulation involves both CRH and AVP. Unlike CRH which participates also in the maintenance of basal ACTH and glucocorticoids secretion, the role of AVP appears to be limited to corticotropic response to stress.