[Predictive factors of spontaneous pregnancies among women with diminished ovarian reserve patients treated with DHEA]. / Facteurs prédictifs de grossesse spontanée chez les femmes présentant une réserve ovarienne diminuée traitées par DHEA.

INTRODUCTION: Diminished ovarian reserve remains a challenge in the reproductive medicine field. Treatment options for these patients are limited and there is no consensus to make any recommendations. Regarding adjuvant supplements, DHEA could play a role in follicular recruitment and, therefore, may increase spontaneous pregnancy rate. MATERIALS AND METHODS: This study was a monocentric historical and observational cohort study carried out in the reproductive medicine department at the University Hospital, Femme-Mère-Enfant in Lyon. All women presenting with a diminished ovarian reserve treated with 75mg/day of DHEA were consecutively included. The main objective was to evaluate the spontaneous pregnancy rate. The secondary objectives were to identify predictive factors for pregnancy and the evaluation of treatment side effects. RESULTS: Four hundred and thirty-nine women were included. In all, 277 were analyzed, 59 had a spontaneous pregnancy (21.3%). The probability of being pregnant was respectively 13.2% (IC95 9-17.2%), 21.3% (IC95 15.1-27%) and 38.8% (IC95 29.3-48.4%) at 6, 12 and 24 months. Only 20.6% of patients complained of side effects. CONCLUSION: DHEA may improve spontaneous pregnancies in women with diminished ovarian reserve without any stimulation.

Comparative effectiveness of gonadotropins used for ovarian stimulation during assisted reproductive technologies (ART) in France: A real-world observational study from the French nationwide claims database (SNDS).

This comparative non-interventional study using data from the French National Health Database (Système National des Données de Santé) investigated real-world (cumulative) live birth outcomes following ovarian stimulation, leading to oocyte pickup with either originator recombinant human follicle-stimulating hormone (r-hFSH) products (alfa or beta), r-hFSH alfa biosimilars, or urinaries including mainly HP-hMG (menotropins), and marginally u-hFSH-HP (urofollitropin). Using data from 245,534 stimulations (153,600 women), biosimilars resulted in a 19% lower live birth (adjusted odds ratio (OR) 0.81, 95% confidence interval (CI) 0.76-0.86) and a 14% lower cumulative live birth (adjusted hazard ratio (HR) 0.86, 95% CI 0.82-0.89); and urinaries resulted in a 7% lower live birth (adjusted OR 0.93, 95% CI 0.90-0.96) and an 11% lower cumulative live birth (adjusted HR 0.89, 95% CI 0.87-0.91) versus originator r-hFSH alfa. Results were consistent across strata (age and ART strategy), sensitivity analysis using propensity score matching, and with r-hFSH alfa and beta as the reference group.

[Comparison of oral dydrogesterone with micronized vaginal progesterone in fresh embryo transfert in IVF/ICSI]. / Comparaison de la dydrogestérone avec une progestérone micronisée vaginale dans le transfert d'embryon frais en FIV/ICSI.

INTRODUCTION: Luteal insufficiency corresponds to a progesterone deficiency affecting women who receive treatment for in vitro fertilization (IVF). Different routes of progesterone administration exist and have varying degrees of acceptability to patients. The aim of this study was to compare two luteal phase support (LPS) treatments: oral dydrogesterone versus micronized vaginal progesterone on the clinical pregnancy occurrence after fresh embryo transfer. MATERIAL AND METHODS: This study was a monocentric historical and observational cohort study carried out in the reproductive medicine department at the University Hospital, Femme Mère Enfant in Lyon. All the data were collected retrospectively. Women between 18 and 43 years old, who completed an IVF cycle with or without ICSI, followed by fresh embryo transfer on the second or third day after oocyte retrieval (D2 or D3) or at the blastocyst stage (D5 or D6) between July 2019 and July 2020 were included. The 290 patients included between July 2019 and January 2020 received 600mg per day of PMV. The 290 patients in the OD group included between January and July 2020 received 30mg OD per day. RESULTS: In the univariate analysis, the clinical pregnancy occurrence per transfer was comparable between the MVP and OD groups (P>0.05) (OR [95% CI]): 0.904 [0.630 ; 1.296]. In the multivariate analysis, OD also appeared to be associated with a similar pregnancy occurrence compared to MVP, with a non-significant difference (OR [95% CI]): 0.940 [0.640; 1.380]. The use of OD compared to MVP did not significantly influence the clinical pregnancy occurrence in any age group. There was no significant difference between the two groups in the clinical pregnancy occurrence, whether the patients belonged to the reference population of the center or not (P>0.05) (OR [95% CI]): 2.367 [0.568; 3.568]. CONCLUSION: This important French retrospective study confirms the safety and efficacy of OD.

Motivations and personality characteristics of candidate sperm and oocyte donors according to parenthood status: a national study from the French CECOS network.

STUDY QUESTION: In a non-commercial national gamete donation programme, do the motivations and personality characteristics of candidate sperm and oocyte donors differ according to their parenthood status? SUMMARY ANSWER: Moderate differences exist between non-parent and parent candidate donors in motivations for gamete donation and representations as well as in personality characteristics. WHAT IS KNOWN ALREADY: Several studies have analysed the motivations and experiences of oocyte or sperm donors, but mainly in countries where gamete donation is a commercial transaction, and very few studies have reported results of personality traits using personality inventory tests. No study has specifically investigated the motivations and personality characteristics of candidate gamete donors according to parenthood status. STUDY DESIGN SIZE DURATION: A prospective study was carried out including 1021 candidate donors from 21 centres (in university hospitals) of the national sperm and egg banking network in France between November 2016 and December 2018. PARTICIPANTS/MATERIALS SETTING METHODS: In total, 1021 candidate gamete donors were included in the study. During their first visit, male (n = 488) and female candidate donors (n = 533) completed a questionnaire on sociodemographic characteristics, their motivations for donation and their representations of donation, infertility and family. Secondly, a NEO Personality Inventory (NEO-PI-R) exploring the Big Five personality traits was completed online. Results were compared between parent and non-parent candidate donors. MAIN RESULTS AND THE ROLE OF CHANCE: Altruistic values were the principal motive for donation irrespective of parenthood status. Reassurance about their fertility or preservation of sperm for future use was more often reported in non-parent than in parent candidate donors. With regard to representation of gamete donation or of the family, independently of their parenthood status, candidate donors more frequently selected social rather than biological representations. Mean personality characteristics were in the normal range. Non-parent candidate donors had higher scores on openness and depression than parents, while parent candidate donors appeared more social than non-parents. LIMITATIONS REASONS FOR CAUTION: The personality characteristics inventory was not completed by all candidate donors included in the study. However, family status did not differ between the two groups (NEO-PI-R completed (n = 525) or not), while the group who completed the NEO-PI-R had a higher educational level. This national study was performed in a country where gamete donation is subject to strict legislation. WIDER IMPLICATIONS OF THE FINDINGS: In a global context where reproductive medicine is commercialized and gamete donor resources are limited, this study found that altruism and social representations of gamete donation and family are the main motivations for gamete donation in a country which prohibits financial incentive. These findings are relevant for health policy and for gamete donation information campaigns. STUDY FUNDING/COMPETING INTERESTS: Grant from the Agence de la Biomédecine, France. The authors have nothing to disclose related to this study. TRIAL REGISTRATION NUMBER: N/A.

[Vaginal hysterectomy using electrofusion: a study of 96 cases]. / Hystérectomie vaginale par électrofusion: étude sur 96 cas.

OBJECTIVE: To compare ligature by electrofusion versus sutures in the practice of vaginal hysterectomy. STUDY DESIGN: This is a retrospective study on 96 patients completed over a period of 47 months. Patients were allocated into two groups: the electrofusion "suture-free" group (n=54) and the "suture" control group (n=42). Designed-end points were operating time, postoperative pain, duration of postoperative hospitalization and perioperative complications. RESULTS: In the electrofusion group, the operating time was significantly reduced (51.3+/-22.6 min versus 67.6+/-20.1 min) as well as the reported postoperative pain (based on the visual analog scale - VAS) (1.9+/-2.0 versus 3.5+/-2.3). The average morphine consumption rate and the timing of postoperative morphine administration were lower in the electrofusion group (22.4+/-31.0mg versus 45.4+/-51.3 mg and 22.4+/-13.4 h versus 29.4+/-18.8 h, respectively). Moreover, in the electrofusion group there was less need for additional analgesics (1.9+/-2.0 versus 3.5+/-2.3) and the hospital-stay was shorter (4.2+/-1.3 days versus 5.0+/-1.0 days). There was no significant difference between the two groups in regard to perioperative complications. CONCLUSION: The use of electrofusion in vaginal hysterectomy appears to be a reliable ligation technique which reduces significantly the operating time, the postoperative pain and the length of postoperative hospitalization.

The impact of histones linked to sperm chromatin on embryo development and ART outcome.

The purpose of this study was to investigate the relationship between the proportion of sperm chromatin linked to remaining histone and assisted reproductive technology (ART) outcome. A prospective cohort study was performed on couples undergoing ART process at the Department of Reproduction Medicine (HFME, Bron, France). The histone-to-protamine ratio (HPR) was measured using the method described by Wykes & Krawetz (2003) J Biol Chem 278, 29471. The correlations with sperm DFI, blastocyst formation, pregnancy rate, and delivery rate were investigated. A total of 291 ART cycles were included (42 c-IVF and 249 ICSI procedures): 3870 oocytes were punctured and 2211 embryos were obtained, among which 507 were transferred and 336 frozen. The mean HPR was 18.9%. A significant negative correlation was found between HPR and DFI (r = -0.12, p < 0.05). Regarding the type of ART procedure (c-IVF or ICSI), the same kind of relationship between HPR and ART parameters was observed. Regardless of the type of ART procedure used, when the HPR was within the range [6%; 26%], the blastocyst formation rate was higher: 87.8% vs. 71.2% (HPR<6%; p < 0.01) and 74.6% (HPR >26%; p < 0.01). The highest delivery rate (DR; 24.5%) was obtained for HPR within the range [6%; 26%]; DR was 21.9% for HPR<6% and 18.3% for HPR>26%; however, the differences were not statistically significant. The procedure described in this study seems to be a reliable evaluation of the HPR. The HPR parameter seems to be correlated to embryonic development up to the blastocyst stage, but its involvement in clinical pregnancy/delivery could not be confirmed. HPR should be further investigated for confirming the relationship with blastocyst formation. After this, the next step will be to investigate the etiologies of HPR alterations for improving the sperm nucleus quality for increasing the chance of pregnancy.

Geographic variations in probability of pregnancy in four cities of France.

BACKGROUND: Several studies have described geographic variations in human fecundability, but this phenomenon has almost exclusively been studied at an international level rather than within a given country. Our aim was to describe geographic variations in fecundability, the monthly probability of pregnancy, between four cities of France. METHODS: We conducted a cross-sectional study in four French maternity units from Toulouse, Rennes, Lyons and Paris, among partners of pregnant women. Women were asked about the time to pregnancy (TTP) of their current pregnancy. TTP was analysed with a discrete Cox model allowing to estimate fecundability ratios (FR). RESULTS: Time to pregnancy was defined for 894 couples. There was no strong evidence of heterogeneity in fecundability between the four compared cities (p=0.05 without adjustment and p=0.25 after adjustment for behavioural and medical factors). The highest fecundability was observed in Rennes and the lowest in Toulouse (fecundability ratio (FR)=1.28, 95% CI: 1.01-1.63). Differences in fecundability were smaller between the other cities. CONCLUSION: We highlighted a possibly slightly higher fecundability in Rennes compared to Toulouse. Possible explanations for this finding are discussed. We note that the finding is consistent with previous observations indicating a higher sperm concentration among semen donors in Rennes than in Toulouse.

[DNA sperm methylation in assisted reproductive techniques]. / Méthylation du spermatozoïde en Assistance médicale à la procréation (AMP).

In the last few years, many tests were developed to study the fertilizing properties of the spermatozoa. However none of them was useful to obtain a prognostic factor. Indeed, the integrity of the spermatic DNA is also necessary to a successful fertilization for obtaining a pregnancy. DNA integrity could be evaluated by the measurement of the level of DNA methylation. Indeed, in the mammals, the methylation of the ADN is involved in diverse processes amongst them the regulation of the genome expression during the embryonic development. The objective of this study is to evaluate the impact of the level of methylation of the spermatic DNA in the success of in vitro fertilization (IVF), in terms of rate of fertilization, quality of the embryos and rate of pregnancy. The immunostaining of the 5-methylecytosine, then the quantification by image analysis or with flow cytometry, allowed an objective evaluation of the level of total methylation of spermatic DNA. Our data show that the level of DNA methylation influences neither the fertilization rate nor the embryos quality. On the other hand, the rate of pregnancy is decreased if the total level of DNA methylation is lower than a threshold value. The level of spermatic DNA methylation represents a new parameter of spermatic maturation.

Expression of cell cycle regulatory proteins in chronic lymphocytic leukemias. Comparison with non-Hodgkin's lymphomas and non-neoplastic lymphoid tissue.

The expression of certain cell cycle regulatory proteins: cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin E, Bcl2 and PCNA was examined in peripheral blood lymphocytes (PBL) from 25 cases of chronic lymphocytic leukemias (CLL) in order to analyze a possible cell cycle involvement of CLL lymphocytes. For comparison, we also studied the expression of these proteins in: 23 samples of non-Hodgkin's lymphoma (NHL) tissue of different histological types, 10 samples of non-neoplastic lymphoid tissue (NLT), non-stimulated PBL (NS-PBL) and PHA-stimulated PBL (PHA-PBL) from three healthy donors. Samples were lysed and proteins were resolved on polyacrylamide gel followed by Western blot. The expression of cdk4 and cyclin E, both known to act in early cell cycle stage, was approximately on the same level in all groups of lymphoid pathology examined. In particular, we found that that 19 out of 24 CLL cases were cyclin E positive and all but one were cdk4 positive, ie they expressed these markers over twice the level of non-stimulated healthy PBL. The cdk1 expression was above the level seen in NS-PBL in 14 (56%) cases, but the average expression was significantly lower than in the other tissues examined, including low-grade lymphomas. Cdk2 expression was comparable in CLL and in low malignancy grade NHL, but weaker than in other NHL and in NLT. Cyclins A and B, normally observed in advanced cell cycle phases, were not seen in any CLL case. The presence of cdk4 and cyclin E in the blood cells of the majority of CLL cases studied, as well as cdk1 and cdk2 in some cases, indicate that the CLL cells are not quiescent, but are blocked in an early stage of the G1 cell cycle phase, and/or that the expression of these proteins is pathologically deregulated.

[Administering GnRH Agonists in the luteal phase of Artificial Cycle Frozen-Thawed Embryo Transfers. A prospective randomized study]. / Administration d'agonistes de la GnRH (Gonadotrophin Releasing Hormone) en phase lutéale des protocoles substitutifs de transferts d'embryons congelés: étude prospective randomisée.

OBJECTIVE: Adding GnRH agonists in the luteal phase has recently been said to improve implantation in IVF treatment (increased rates of pregnancy and birth). Adding GnRH agonists could also be beneficial for frozen-thawed embryo transfers. The objective was to compare the administration of Gonadotropin Releasing Hormone (GnRH) agonists during implantation with usual progesterone supplementation in the artificial cycle of frozen-thawed embryo transfers. METHODS: A prospective randomized controlled trial was conducted in a reproductive medicine center in a university hospital including all women starting an artificial cycle of Frozen-Thawed Embryo Transfers (FET). Two hundred and twenty women were randomized from September 2013 to June 2014. In the addition of GnRh agonists' group, two triptorelin injections of 0.1mg were carried out on the 4th day and on the 6th day following the introduction of progesterone. The primary outcome was the ongoing pregnancy rate. RESULTS: The ongoing pregnancy rate was higher (17 % versus 10.6 % P=0.29) when triptorelin was added, although the difference wasn't significant for the population as a whole. The increase proved to be significant in the case of day 2 embryos (34.6 % versus 10.3 % P<0.05) and of vitrified blastocysts (33.3% versus 12.5% P<0.05). CONCLUSION: The ongoing pregnancy rate for day 2 embryos and vitrified blastocysts significantly increased when GnRH agonists were added during implantation.

Maternal humoral factors associated with perinatal human immunodeficiency virus type-1 transmission in a cohort from Kigali, Rwanda, 1988-1994.

OBJECTIVES: to study different parameters of humoral immunity responses in the serum of 39 human immunodeficiency virus type-1 infected pregnant women from Kigali, (Rwanda) in correlation with perinatal transmission. METHODS: this study was done between 1988 and 1994. Thirty nine HIV-1 infected women, 18 transmitting (T) and 21 non-transmitting (NT) mothers, have been chosen based on the quantity of sera available for analysis. Maternal data were collected at the time of delivery or during the preceding month. Quantification of viral load was performed by the signal amplification bDNA assay. Specific reactivity of antibody was tested against recombinant p24 protein and five different synthetic peptides from gp120 and gp41 based on HIV LAI-strain sequences. Neutralization assays were performed against laboratory (RII strain of the HIV-1 C subtype) and primary strains (two NSI and one SI of the HIV-1 A subtype). Antibody Dependent Cellular Cytotoxicity assay was performed with CEM.NK(R) cells against a laboratory HIV-1 strain. RESULTS: absence of correlation regarding maternal viral load, or viral subtype and vertical transmission was observed. By contrast, the CD4/CD8 ratio was significantly higher in non-transmitting mothers compared to transmitting mothers. Moreover, high anti-p24 antibody avidity was correlated with a lower risk of perinatal transmission. Furthermore, transmission risk appeared significantly higher with reactivity of serum samples to linear epitopes of gp41 (amino acids 566-582, 578-594), whereas risk appeared lower with reactivity to the immunodominant domain of gp41 (amino acids 597-609). No significant difference was observed in titres of antibody neutralizing primary isolates (two NSI (non syncitium inducer) and one SI (syncitium inducer) of the HIV-1 A subtype) and laboratory strain (RII strain, of the HIV-1 C subtype) between transmitting and non-transmitting mother's sera. In addition, titres of Antibody Dependent Cellular Cytotoxicity were similar in transmitting versus non-transmitting mothers. However, high Antibody Dependent Cellular Cytotoxicity titres were correlated with a good clinical status of children. CONCLUSIONS: three parameters such as high CD4/CD8 ratio, high anti-p24 antibody avidity and high reactivity against the immunodominant epitope of gp41 have been shown to be correlated with no perinatal transmission. High Antibody Dependent Cellular Cytotoxicity titres appeared to be linked to a good clinical status of children after birth. One parameter, reactivity against two linear epitopes of gp41, appeared to be correlated with vertical transmission.

Cyclodextrin enhances spermicidal effects of magainin-2-amide.

Magainins are antimicrobial peptides with known spermicidal activity. Their activity is inhibited by cholesterol present in eukaryotic cell membranes. Pretreatment of spermatozoa with methyl-beta-cyclodextrin, which extracts cholesterol from cell membranes and induces capacitation, sensitizes them to magainin-2-amide as shown by a decrease in human sperm motility determined by computer-assisted sperm analysis and a concomitant decrease in sperm viability, as measured by MitoTracker(R) Red CMXRos labeling. Magainin-2-amide affects mainly the fast progressive spermatozoa inducing them directly into an immotile state, without an increase in motile non-progressive and slow progressive spermatozoa. We conclude that methyl-beta-cyclodextrin highly potentiates the deleterious effect of magainin-2-amide on human spermatozoa. Most probably, this effect can be explained by cholesterol extraction from sperm cell membranes.

[Assays for assessment of sperm DNA integrity: relationships with fertility and conceptus quality]. / Tests d'exploration de la qualité nucléaire du spermatozoïde: relations avec la fertilité et la qualité du conceptus.

Several assays are available for testing nuclear quality of spermatozoa, many of them allowing to define a DNA fragmentation index (DFI). Numerous recent studies on this subject agree on several points: negative correlations are observed between DFI and sperm characteristics. Concerning the relationships between DFI and artificial reproductive technologies, there are some disagreements about correlations between DFI and fertilization rates; conversely, in case of high DFI, both blastocyst formation rate and pregnancy rate are significantly reduced. Several authors have defined a threshold value for DFI, corresponding to an absence of pregnancy, or a very low pregnancy rate, for samples above this value. Unfortunately, there are no data available concerning the relationships between sperm DNA quality and abnormalities at birth.

[Laparoscopic Davydov or laparoscopic transposition of the peritoneal colpopoeisis described by Davydov for the treatment of congenital vaginal agenesis: the technique and its evolution]. / Le Davydov coelioscopique ou transposition coelioscopique du colpopoiesis péritonéal pelvien décrit par Davydov pour le traitement des agénésies congénitales du vagin: la technique et son évolution.

INTRODUCTION: The laparoscopic Davydov is described. The data concerning the surgery and the postoperative course are reported at the same time as the data concerning the anatomical and sexological results. PATIENTS AND METHODS: The surgery includes three steps: (i) cleavage under laparoscopic guidance, (ii) peritoneovestibular stitch by perineal approach, (iii) making the vaginal vault with the laparoscope. The cleavage can be performed in front of the fascia interposed between the bladder and the rectum or behind it. A nymphoplasty can be added to the colpopoeisis. RESULTS: Between February 1996 and March 2003 we operated on 28 patients affected by congenital vaginal agenesis using the laparoscopic Davydov technique. Two peroperative complications occurred (urinary tract injuries during the first step: laparoscopic management) and two postoperative complications (intraperitoneal migration of the mould and vesicovaginal fistula managed successfully with the laparoscope for the first one and trough laparotomy for the second one). Four re-operations (incision and dilation) were necessary. The length of the neovagina was, at the last assessment, 7.2 +/- 1.3 cm. The Female Sexual Function Index was 26.5 +/- 5.6 vs. 27.9 +/- 4.5 in a control cohort. In the patients whose cleavage was performed behind the fascia (13 cases vs. 15) no complication occurred, no re-operation was necessary, the length of the neovagina was 7.0 +/- 0.7 cm and the FSFI was 26.3 +/- 5.9. DISCUSSION AND CONCLUSION: The laparoscopic Davydov is, if the dorsal approach is used for the cleavage, an easy to make operation (operating time: 90 +/- 29 minutes) with a short hospital stay. The postoperative care is simple (vaginal mould useless). Heterosexual activity with penile penetration can start early (6 to 8 weeks). The level of satisfaction is high. Laparoscopic Davydov procedure may be considered a good alternative to the more complex ones (as Vecchietti's technique) or to the more dangerous ones (sigmoid colpoplasty).

[Laparoscopic promontofixation: defining early morbidity using a standardized method]. / Promontofixation par cœlioscopie : évaluation de la morbidité précoce par une méthode standardisée.

OBJECTIVE: Adverse event reporting for laparoscopic promontofixation is highly variable and non-standardized in the literature. The aim of this study was to better characterize early postoperative complications of laparoscopic promontofixation for genital prolapse using a standardized reporting methodology. PATIENTS AND METHODS: A retrospective study was conducted on 174 women with genital prolapse undergoing laparoscopic promontofixation from January 2008 to January 2013. Complications arising during the first month after surgery were reviewed according to the Clavien and Dindo classification. RESULTS: At least one postoperative adverse event was reported in 57 out of 174 (33 %) women, grade 1 in 22 patients (13 %), grade 2 in 31 patients (18 %) and grade 3 in 4 patients (2 %). No patient experienced a grade 4 or 5 complication. Fifty-three out of 57 (93 %) complications were grade 1 or 2. The most frequently reported adverse event (n=24; 14 %) was constipation (grade 2). DISCUSSION AND CONCLUSION: Laparoscopic promontofixation is a safe procedure with almost exclusively benign (grade 1 or 2) early complications. The hypothesis of induction or increasing constipation by this type of genital prolapse surgery should be further evaluated.

[Donor sperm insemination after failed intracytoplasmic sperm injection]. / Insémination avec tiers donneur après échec d'ICSI intracouple.

After ICSI intracouple failure, donor sperm insemination (AID) is routinely offered. The prognostic factors and the rate of pregnancy resulting from this procedure are poorly documented (2 papers found). This retrospective study, which was conducted as part of the Federation of CECOS, completes a previous study and shows that female age, ovarian response and sperm characteristics were prognostic factors in obtaining a pregnancy with AID.