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Introduction : Up to 30% of couples may face secondary infertility. The impact of ectopic pregnancy, spontaneous abortion, pregnancy termination or live birth with caesarean section may impair further fertility in different ways. However, secondary infertility after physiological vaginal life childbirth has been little studied. The aim of this study was to describe the population and the fertility issues and analyze the predictive factors of success in in vitro fertilization in women presenting secondary infertility after a physiological vaginal childbirth. Material and methods : This single-centre retrospective study included women aged 18-43 years consulting between 2013 and 2020 for secondary infertility in a couple having already had previous vaginal life childbirth. Couples’ characteristics, management decision after the first consultation and IVF outcomes were analyzed. Results : Secondary infertility was found in 286 couples, out of whom 138 had a history of vaginal life childbirth. Population was characterized by an advanced female age and overweight. After the first consultation, IVF was performed in only 40% of couples. No predictive factor of live birth was found. Conclusion : Our study shows that in couples with secondary infertility after prior physiological delivery cigarette smoking is frequent in male partners, and ovarian reserve markers are altered. However, no statistically significant predictive factor of live birth after IVF treatment has been identified. Further large prospective studies are necessary.

Research question Does mild COVID-19 infection affect the ovarian reserve of women undergoing an assisted reproductive technology (ART) protocol? Design A prospective observational study was conducted between June and December 2020 at the ART unit of Tenon Hospital, Paris. Women managed at the unit for fertility issues by in-vitro fecundation, intracytoplasmic sperm injection (IVF/ICSI), fertility preservation, frozen embryo transfer or artificial insemination, and with an anti-Mullerian hormone (AMH) test carried out within 12 months preceding ART treatment, were included. All the women underwent a COVID rapid detection test (RDT) and AMH concentrations between those who tested positive (RDT positive) and those who tested negative (RDT negative). Results The study population consisted of 118 women, 11.9% (14/118) of whom were COVID RDT positive. None of the tested women presented with a history of severe COVID-19 infection. The difference between the initial AMH concentration and AMH concentration tested during ART treatment was not significantly different between the COVID RDT positive group and COVID RDT negative group (–1.33 ng/ml [–0.35 to –1.61) versus –0.59 ng/ml [–0.15 to –1.11], P = 0.22). Conclusion A history of mild COVID-19 infection does not seem to alter the ovarian reserve as evaluated by AMH concentrations. Although these results are reassuring, further studies are necessary to assess the effect of COVID-19 on pregnancy outcomes in women undergoing ART.

Recurrent implantation failure is defined as the absence of pregnancy after at least three transfers of good-quality embryos after in vitro fecundation/intracytoplasic sperm injection.The aim of this study was to describe a multicentre cohort of women with unexplained RIF, to analyse the factors associated with clinical pregnancy and to evaluate the immunomodulatory therapies efficacy.Women were consecutively recruited from university departments with unexplained RIF.Sixty-four women were enrolled with mean age 36 ± 3 years. The rates of clinical pregnancy in 64 women were compared in untreated and treated cycles and according to therapies used during the last prospectively followed embryo transfer. A clinical pregnancy after the transfer was noted in 56 % pregnancies on intralipids and in 50 % on prednisone, versus 5 % in untreated ones (p0.001). The 340 embryo transfers of these 64 women resulted in 68 clinical pregnancies and 18 live births. Clinical pregnancies were significantly more frequent in treated versus untreated embryo transfers (44 % vs 9 %; p0.001) with odds ratio at 8.13 (95 % CI 4.49-14.72, p0.0001). Cumulative pregnancy rates were higher for steroid-treated transfers than for untreated transfers when considering overall transfers before and after using steroids and also only those under steroids. Cumulative pregnancy rates were not different from steroid- and intralipid-treated embryo transfers CONCLUSIONS: In this multicentre study of women with unexplained RIF, use of immunomodulatory treatments before embryo transfer resulted in higher clinical pregnancy. Randomised, well-designed studies in well-defined population of RIF women are necessary to confirm our preliminary data.

Background PPOS protocols, initially described for FP in women with cancer, have many advantages compared to antagonist protocols. PPOS protocols were not evaluated for women with endometriosis. The objective of the study was to describe fertility preservation outcomes in women with endometriosis and to compare an antagonist protocol with a Progestin-Primed Ovarian Stimulation (PPOS) protocol. Method We conducted a prospective cohort study associated with a cost-effectiveness analysis in a tertiary-care university hospital. The measured outcomes included the numbers of retrieved and vitrified oocytes, and direct medical costs. In the whole population, unique and multiple linear regressions analysis were performed to search for a correlation between individual characteristics and the number of retrieved oocyte. Results We included 108 women with endometriosis who had a single stimulation cycle performed with either an antagonist or a PPOS protocol. Overall, 8.1 ± 6.6 oocytes were retrieved and 6.4 ± 5.6 oocytes vitrified per patient. In the multiple regression model, age (p = 0.001), prior ovarian surgery (p = 0.035), and anti-Mullerian hormone level (p = 0.001) were associated with the number of retrieved oocytes. Fifty-four women were stimulated with an antagonist protocol, and 54 with a PPOS protocol. A mean of 7.9 ± 7.4 oocytes were retrieved in the antagonist group and 8.2 ± 5.6 in the PPOS group (p = 0.78). A mean of 6.4 ± 6.4 oocytes were vitrified in the antagonist group and 6.4 ± 4.7 in the PPOS group (p = 1). In the cost-effectiveness analysis, the PPOS protocol was strongly dominant over the antagonist protocol. Conclusion Fertility preservation procedures are feasible and effective for patients affected by endometriosis. Antagonist and PPOS protocols were associated with similar results but the medico-economic analysis was in favor of PPOS protocols.

We aimed to compare the proportion of peripheral blood natural killer (NK) cells (CD3–CD56+) and T-cell large granular lymphocytes (CD8+CD57+) during preconception in a homogenous group of women with unexplained well-defined recurrent miscarriage (RM) and repeated implantation failure (RIF) vs healthy controls in relation to pregnancy outcomes. This case–control study followed by a literature review and meta-analysis was conducted in three university hospitals. Patients and controls were consecutively recruited from December 2015 to October 2017. In total, 115 women were included in the study: 54 with RM, 41 with RIF and 20 healthy controls with ≥ 2 term births. Percentages of CD3–CD56+ and CD8+CD57+ cells and sub-populations of CD3–CD56+ cells did not differ between cases and controls. The results for women with subsequent miscarriage did not differ from those with live births. The meta-analysis of the literature showed higher NK-cell proportions in RM [mean difference 3.47 (95% CI 2.94–4.00); p

Artificial Intelligence (AI), a concept which dates back to the 1950s, is increasingly being developed by many medical specialties, especially those based on imaging or surgery. While the cognitive component of AI is far superior to that of human intelligence, it lacks consciousness, feelings, intuition and adaptation to unexpected situations. Furthermore, fundamental questions arise with regard to data security, the impact on healthcare professions, and the distribution of roles between physicians and AI especially concerning consent to medical care and liability in the event of a therapeutic accident.

Introduction Echecs d’implantation (EI) a repetition sont definis comme l’absence de grossesse apres un transfert de ≥ 3 embryons de bonne qualite [1] . Fausses couches (FCS) a repetition sont definies comme antecedent ≥ 3 FCS precoces [2] . L’objectif de cette etude etait de caracteriser cliniquement et biologiquement la population de femmes consultant 3 centres hospitaliers Est-Parisiens pour FCS ou/et EI repetes. Patients et methodes Au total, 147 femmes âgees de 18 a 45 ans ayant un antecedent d’au moins 3 FCS precoces et/ou au moins 3 embryons transferes sans grossesse obtenue et sans etiologies evidentes retrouvees ont ete recrutees dans les services de Medecine interne ; Gynecologie obstetrique et de medecine de la reproduction. Les donnees cliniques recueillies concernaient l’âge, existence d’une maladie auto-immune ou d’une pathologie pouvant interferer avec la fertilite (endometriose, atteinte tubaire), l’existence de surpoids IMC > 25, le nombre de grossesses, d’embryons transferes, de FCS et d’accouchements a terme. Les donnees biologiques recueillis comportaient le taux de l’AMH, la TSH, la proteine C, la proteine S, l’antithrombine III, les mutations des facteurs V de Leyden et du facteur II, les autoanticorps les anticorps antinucleaires, anti-ADN natifs, anti-ECT, anti-cardiolipides et anti-β2GP1 (β-2-glycoproteine 1) Ig G et IgM, anti-TPO et anti-TG et anti-transglutaminases et les anticorps antiphospholipides non conventionnels (anti-phosphatidylethanolamines IgG–PEG et M–PEM, les anti-PS/PT IgG et M, les anti-annexine V IgG–AA5). Resultats Dans le groupe de 88 femmes avec FCS a repetition l’âge moyen etait de 35 ans (± 5 ans), le nombre des grossesses etait de 6 (4–7), de FCS 4 (4–6) et d’accouchements 1 (0–1). Parmi ces femmes 40 (45 %) etaient nulligeste, 8 (9 %) presentaient une maladie auto-immune dont une thyroidite avec les taux d’anticorps anti-TPO et anti-TG eleves chez 6 (8 %) et 4 (5 %) patientes, respectivement. Douze femmes (14 %) avaient un surpoids, 2 (2 %) une endometriose et 1 (1 %) une atteinte tubaire. Le taux d’AMH etait de 1,81 (1,21–3,30), TSH 1,77 (1,25–2,19). Dans le groupe de 59 femmes avec EI a repetition l’âge moyen etait de 36 ans (± 4 ans), le nombre des grossesses etait de 1 (0–3), de FCS 0 (0–1), d’embryons transferes 6 (5–8) et d’accouchements 0 (0–0). Parmi ces femmes 13 (23 %) presentaient une maladie auto-immune dont une thyroidite avec les taux d’anticorps anti-TPO et anti-TG eleves chez 11 (20 %) et 4 (8 %) patientes, respectivement. Sept femmes (12 %) avaient un surpoids, 8 (14 %) une endometriose et 9 (16 %) une atteinte tubaire. Le taux d’AMH etait de 2,10 (1,10–3,50), TSH 1,89 (1,20–2,71). Le bilan de thrombophilie etait normal dans les deux groupes, y compris la recherche d’APL conventionnels. Les anticorps ANF etait positifs chez 22 femmes (28 %) dans le groupe FCS et 17 (32 %) dans le groupe EI sans aucune specificite, des APL non conventionnels ont ete note dans 12 cas (anticorps anti-AA5 et anti-PEG chez une patiente (1 %) dans le groupe FCS et anti-PEM chez 5 femmes dans le groupe FCS (8 %) et 5 (12 %) dans les groupe EI). Conclusion Dans cette etude concernant les femmes avec des FCS et EI inexpliques, la prevalence des marqueurs immunologiques restent faibles et d’autres marqueurs sont necessaires a developper.

Endometriosis is a common condition, causing pain and infertility. In infertile woman with superficial peritoneal endometriosis and patent tubes, laparoscopy is recommended, followed by ovarian stimulation alone or in combination with intrauterine inseminations. In case of ovarian or deep endometriosis, the indications of surgery and assisted reproductive technologies remain to be defined precisely. In vitro fertilization is generally proposed after the failure of up to three inseminations, directly for ovarian or deep endometriosis, or in case of an associated factor of infertility, mainly male. Before ovarian stimulation in view to in vitro fertilization, a pretreatment by GnRH agonist for 2 to 6 months or combined contraceptive for 6 to 8 weeks would improve the pregnancy rate. Egg donation is effective in patients with advanced ovarian failure or lack of ovarian response to stimulation. Fertility preservation, especially by oocytes vitrified, must be proposed preventively to women with endometriosis at risk of ovarian failure, without close wish to be pregnant.

Deep infiltrating endometriosis is the most severe form of the disease, defined by infiltration beneath the peritoneum greater than 5mm. It affects several anatomical locations including the bladder, the vesico-uterine cul-de-sac, the torus uterinum, the uterosacral ligament, rectovaginal septum and the colon-rectum. Deep infiltrating endometriosis is associated with infertility. Surgery performed for deep infiltrating endometriosis in the context of pain offers good pregnancy rates either spontaneously or after assisted reproductive technologies. The results are less favorable when digestive tract is involved. IVF performed in the context of deep infiltrating endometriosis allows very satisfactory results and does not entail risks of aggravation of the pathology. There is currently no clear evidence to support either IVF or surgery to manage infertility associated with deep infiltrating endometriosis, but patients should be informed, although a risk of severe complication exists, that surgery is the only way to increase the chances of spontaneous fertility.

Introduction L’equilibre immunitaire est essentiel dans l’implantation embryonnaire et dans le maintien de la grossesse. La rupture de cet equilibre pourrait etre responsable d’echecs d’implantation (EI) et de fausses couches spontanees (FCS) inexpliquees a repetition. Parmi les cellules immunitaires impliquees, les lymphocytes Natural Killers (CD3-CD56 + ) et les grands lymphocytes granuleux T (CD3 + CD8 + CD57 + ) peuvent occuper une place importante. L’objectif de ce travail etait d’evaluer la frequence des lymphocytes CD3-CD56+ et T CD3 + CD8 + CD57+ sanguins en preconception chez les femmes presentant des FCS et des EI a repetition. Patients et methodes Le pourcentage des lymphocytes CD3-CD56 + et T CD3 + CD8 + CD57+ sanguins et les sous-populations des lymphocytes CD3-CD56+ immature (CD3-CD56brightCD16-), mature (CD3-CD56dimCD16 + ) et activee (CD3-CD56dimCD16 + CD57 + ) ont ete analyses par cytometrie en flux chez 54 femmes avec des FCS et 41 femmes avec des EI a repetition et compares aux 20 femmes temoins âgees de moins de 45 ans ayant eu ≥ 2 grossesses normales menees a terme. Resultats Les pourcentages des lymphocytes CD3-CD56+ et CD3 + CD8 + CD57+ n’etaient pas differents entre le groupe FCS ou EI et les controles (9,4 % [2,5–31,6], 9,4 % [4,3–29,3] et 10,6 % [3,4–20,2], (p = 0,43) et 5,4 % [0,4–14,4] et 4,3 % [0,0–18,4] vs 3,8 % [0,3–9,7], p = 0,22, respectivement). De la meme facon, la frequence des sous-populations de CD3-CD56+ n’etait pas differente entre le groupe FCS ou EI et les controles (CD3-CD56brightCD16- : 6,7 % [0,0–19,6], 8,1 % [0,0–23,0] et 5,8 % [2,0–18,9], p = 0,18 ; CD3-CD56dimCD16 + : 93,3 % [80,4–100,0], 91,9 % [77,0–100,0] et 94,3 % [81,1–98,0], p = 0,18 ; CD3-CD56dimCD16 + CD57 + : 48,6 % [17,7–85,0], 49,6 % [18,2–80,9] et 45,2 % [28,2–77,2], p = 0,75). Les resultats des femmes avec des fausses couches ulterieures n’etaient pas statistiquement differents des femmes ayant eu ulterieurement des naissances vivantes dans le groupe FCS et le groupe EI (9,8 % [3,2–31,6] vs. 9,4 % [4,1–15,6], p = 0,7 ; 7,8 % [5,2–26,6] vs. 9,6 % [4,4–18,8], p = 0,39, respectivement). Conclusion La proportion de lymphocytes CD3-CD56 + et CD3 + CD8 + CD57+ sanguins dans la periode pre-conceptionnelle ne reflete pas le risque d’echec d’implantation ou de fausse couche. D’autres etudes prospectives sont necessaires afin d’identifier des marqueurs sanguins fiables de desequilibre immunologique dans les FCS et EI a repetition.

Background: To evaluate the impact of the association of endometrioma with or withoutdeep infiltrating endometriosis (DIE) after a first intra cytoplasmic sperm injection- invitro fertilization (ICSI-IVF) cycle on pregnancy rate.Materials and Methods: In this retrospective study, women with endometrioma whounderwent a first ICSI-IVF cycle from January 2007 to June 2010 were reviewed forpregnancy rate. The main outcome measure was the clinical pregnancy rate. A multiplelogistic regression (MLR) was performed; including all variables that were correlatedto the conception rate. Only independent factors of pregnancy rate were included in aRecursive Partitioning (RP) model.Results: The study population consisted of 104 patients (37 without DIE and 67 patientswith associated DIE). Using multivariable analysis, a lower pregnancy rate was associatedwith the presence of DIE (OR=0.24 (95% CI: 0.085-0.7); p=0.009) and the use ofICSI (OR=0.23 (95% CI: 0.07-0.8); p=0.02). A higher pregnancy rate was associatedwith an anti-mullerian hormone (AMH) serum level over 1 ng/ml (OR=4.3 (95% CI:1.1-19); p=0.049). A RP was built to predict pregnancy rate with good calibration [ROCAUC (95% CI) of 0.70 (0.65-0.75)].Conclusion: Our data support that DIE associated with endometrioma in infertilepatients has a negative impact on pregnancy rate after first ICSI-IVF cycle. Furthermore,our predictive model gives couples better information about the likelihood ofconceiving.

Resume Objectif Au cours des fecondations in vitro (FIV) classiques, 5 % des tentatives se soldent par un echec de fecondation imprevisible, du fait d’une absence d’anomalies des parametres spermatiques. Dans 56 % des cas, aucune cause ovocytaire evidente n’est retrouvee. On observe, par contre, un defaut ou une absence de fixation des spermatozoides a la zone pellucide (ZP). Cette etude a pour objectif de preciser les causes moleculaires d’origine spermatique des echecs de FIV, qui sont a ce jour imprevisibles d’apres les donnees de la spermiologie classique. Patientes et methodes Le profil d’expression proteique des spermatozoides de sujets, presentant un echec complet de fecondation et un defaut de fixation des spermatozoides a la ZP, est compare a celui de temoins (hommes a sperme normal et fecondant, participant a une FIV d’indication tubaire). Pour cela, les echantillons de sperme sont analyses par la technologie d’electrophorese 2 Dimensional Electrophoresis-Differential In Gel Electrophoresis (2D-DIGE) avec au prealable une etape de pre-fractionnement des extraits proteiques selon leur point isoelectrique (fraction acide, intermediaire et basique). Resultats Sept proteines differentiellement exprimees chez tous les cas et chez tous les temoins ont ete mises en evidence dans la fraction acide et sept dans la fraction basique. Douze d’entre elles ont ete identifiees par spectrometrie de masse, dont deux (le recepteur a la laminine LR67 et la L-xylulose reductase) ont deja fait la preuve de leur implication dans l’interaction gametique. Discussion et conclusion Ces proteines meritent des investigations complementaires visant a determiner si certains echecs de fecondation en FIV sont causes par des anomalies au niveau de leur expression.

BACKGROUND: Conflicting results have been published about the determinants of pregnancy after oocyte donation (OD). We used the OD model to determine predictive factors of pregnancy in the recipient after frozen-thawed embryo transfer (FTET) in a specific series where all the embryos were cryopreserved without any prior selection for fresh transfer. METHODS: We report a retrospective study in a university tertiary care center. Multivariate analysis and logistic regression were used to identify predictive factors of pregnancy in a series of 450 OD FTET cycles in 198 infertile women between January 1992 and December 2006. RESULTS: The mean (± SD) recipient age was 35.7 (± 4.5). Impaired ovarian function was the main indication for OD. The mean ± SD (range) number of embryos transferred was 1.65 ± 0.5 (1-3). Overall clinical pregnancy, implantation and delivery rates were 30, 18 and 23%, respectively. After univariate analysis, pregnancy rates were significantly higher in recipients under 35 years, in women with a body mass index (BMI)

Performance and security questions in human oocyte cryopreservation have been taking researchers for about two decades. Oocytes are usually frozen at metaphase II. Immature oocytes cryopreservation is still a research alternative. Two techniques are currently available for oocyte cryopreservation: slow freezing and vitrification. Experimental data suggest that vitrification has less impact on oocyte physiology than classical slow freezing. After slow freezing of mature oocytes, survival and fertilization rates reach 70 to 80% whereas cleavage rates are around 90%, leading to five implantations and 1.2 births per 100 thawed oocytes. After vitrification of mature oocytes, survival and cleavage rates reach 90% leading to 11 implantations and 1.8 births per 100 thawed oocytes. The obstetrical and neonatal prognosis of these pregnancies is reassuring. No increased risk of congenital anomalies has been observed. However, further evaluation is needed to guarantee the safety of cryopreservation procedures. Immature oocyte cryopreservation is not currently perfected but some indications appear of great interest.

In elongating spermatids, human sperm chromatin undergoes a complex compaction in which the transition proteins are extensively replaced by the protamine proteins. Several human studies demonstrate that expression of the protamine proteins is altered in some men with male infertility. For this study, we screened the PRM1 (protamine 1) gene for mutations in a large cohort of 281 men seeking infertility treatment. We identified the c.102G>T transversion that results in an p.Arg34Ser amino acid change in two men. One of these patients presented with oligozoospermia associated with increased sperm DNA fragmentation. The second individual was normospermic but together with his partner sought treatment for idiopathic couple infertility. We also identified a novel missense mutation (c.119G>A, p.Cys40Tyr) in a man with oligoasthenozoospermia. These mutations were not observed in control populations. Interestingly, we also detected variants both 5' and 3' to the PRM1 open-reading frame specifically in infertile individuals. Four individuals with unexplained severe oligozoospermia were heterozygote for a c.-107G>C change that is located at -15 bp from the transcription initiation site of the gene. This mutation may influence PRM1 expression. In addition, a c.*51G>C variant was detected in the 3'UTR of PRM1 specifically in a man with severe oligoasthenozoospermia.

International audience; Objective: To identify the male molecular causes of failures of IVF (with a deficient binding of spermatozoa to the zona pellucida, without any obvious oocyte anomaly), which are undetected by classical sperm analysis. Design: Case-control prospective study. Setting: University hospital. Patient(s): Proteomic profiles of spermatozoa in patients with a complete failure of fertilization and no spermatozoa bound to the zona pellucida were compared with those of controls (men with normal fertilization and cleavage rates after classical IVF for tubal indication). Intervention(s): All samples were analyzed by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) after being divided into three fractions according to their isoelectric point. Main Outcome Measure(s): Differentially expressed proteins between infertile men and controls were identified by mass spectrometry. Result(s): Seventeen proteins differentially expressed between cases and controls were found. Twelve of these proteins were identified by mass spectrometry, and two may influence gametes interaction: laminin receptor LR67 and L-xylulose reductase (P34H). Conclusion(s): This study shows that 2D-DIGE might be useful in finding potential targets for diagnosis and prognosis of idiopathic infertility in IVF.

A 37-year-old woman had a histologically documented occipitovertebral metastasis from an invasive epidermoid carcinoma of the uterine cervix. The metastasis was found 3 months after the primary and was treated by local radiation therapy followed by systemic chemotherapy. Radiation therapy was highly effective in relieving the pain but was not associated with changes in magnetic resonance imaging findings. Lymph node involvement and local extension occurred. The patient died 1 year after the diagnosis of the metastasis. Involvement of the occipitovertebral junction by uterine cervix carcinoma metastasis is exceedingly rare. The relevant literature is reviewed.

Resume Les auteurs rapportent la survenue, chez une femme de 37 ans, d’une metastase osseuse occipitovertebrale d’un carcinome epidermoide invasif du col de l’uterus, confirmee histologiquement, decouverte trois mois apres le cancer du col, traitee par radiotherapie locale puis chimiotherapie generale. La radiotherapie a ete efficace sur les douleurs, meme si elle n’a pas modifie les images IRM. La chimiotherapie a ete entreprise. Mais des metastases ganglionnaires, une extension des lesions locales sont survenues et la patiente est decedee a peine plus d’une annee apres la decouverte de la metastase osseuse. Une revue de la litterature est faite a l’occasion de cette localisation exceptionnelle de metastases d’un cancer du col uterin.

RESUME Il s’agit de l’exemple type des problemes poses par la medecine moderne. Nous avons mene a l’Hopital Tenon a Paris, entre 1994 et 1999, une etude retrospective interessant 177 transferts d’embryons congeles puis decongeles chez 139 patientes parmi les 300 demandeuses d’un don d’ovocytes pendant cette meme epoque. Ceci nous conduit a bien souligner les difficultes ethiques creees par la promulgation des lois de bioethique de 1994. C’est ainsi que deux consequences sont devenues evidentes : la penurie de plus en plus grande de donneuses et la necessite de ne transferer que des embryons congeles/decongeles due au decret de 1996 sur la Securite Sanitaire, qui impose une quarantaine des dits embryons pendant 6 mois. En contrepartie, l’emploi de cette methode a apporte de nouvelles informations sur l’implantation et souligne l’importance de la qualite de l’embryon qui est tres etroitement correlee a l’âge de la donneuse.

Human embryo cryopreservation represents an indispensable extension of in-vitro fertilization (IVF) programmes as long as they are based upon the recovery of a large number of oocytes. The most widely used procedures include the cryopreservation of human zygotes or embryos in early cleavage, using 1,2-propanediol and sucrose as cryoprotectants. Our results over a 10 year period (1986-1995) on 5032 thawed cycles involving 14 222 stored embryos make it possible to appraise the results and the contribution of embryo freezing to assisted reproduction. Embryos survived the freeze-thaw process in 73% of cases leading to 4590 transfers of 2.2 embryos (91% of thawed cycles). The clinical pregnancy rate per transfer was 16%, the live birth rate 12%, and the rate of babies born alive per transferred embryo was 6%. Embryo freezing monitored 10 years later produced an average of 8% of additional births. By then, 86% of stored embryos had been thawed for transfer to patients. Destruction or donation were required for only 8% of all frozen embryos and there was no news from the parental couple in relation to almost 6% of embryos. The fate of the vast majority of embryos was decided during the first 5 years of storage. Blastocyst cryopreservation is making new strides, thanks to co-culture systems and embryo selection. Micromanipulation procedures seem to have little impact on the outcome of embryo freezing. Human oocyte freezing is again clinically applied. Indeed, much of the concern about injuries to the oocyte structures through the freeze-thaw process do not seem to be justified, and the problems with frozen-thawed oocyte fertilization has been overcome using intracytoplasmic sperm injection (ICSI). As long as oocyte in-vitro maturation is not well controlled, better results will probably be obtained with mature oocyte cryopreservation. Emerging methods include the freezing of immature oocytes, follicles and ovarian tissue.

Angiotensin converting enzyme (ACE) is a metalloprotease with two isoforms. The somatic isoform is a key component of the renin-angiotensin system; its main function is to hydrolyse angiotensin I into angiotensin II. The germinal or testicular isoform (tACE) located at the plasma membrane of the spermatozoa, plays a crucial role in the spermatozoa-oocyte interaction during in vivo fertilization, in rodents. Disruption of the tACE in mice has revealed that homozygous male tACE-/- sire few pups despite mating normally. Few spermatozoa from these tACE-/- mice are bound to the zona pellucida (ZP) despite normal semen parameters. Based on these findings in mice models, we hypothesized that some infertile men that have the same phenotype as the tACE-/- mice, ie normal semen parameters and a lack of sperm bind to the ZP in vitro, may have a tACE defect.Twenty four men participated to this study. The case subjects (n = 10) had normal semen parameters according to the WHO guidelines (WHO 1999) but a total in vitro fertilization failure with absence of sperm fixation to the ZP. The control subjects (n = 14) also had normal semen parameters and a normal fertilization rate ≥65%. We investigated the tACE expression in spermatozoa by Western-Blot and performed a DNA sequencing of the tACE gene.Three case-subjects and one control-subject had no tACE expression. There were no statistic differences between the two groups. No mutation was detected in the tACE DNA sequence.Our results didn't show any involvement of tACE in human fertilization especially in ZP binding.L’enzyme de conversion de l′angiotensine (ACE) est une métalloprotéase qui se présente sous deux isoformes. Une isoforme somatique qui intervient dans la régulation de la pression artérielle via le système rénine-angiotensine et une isoforme testiculaire spermatique (ACEt) qui interviendrait dans la fixation du spermatozoïde aux enveloppes ovocytaires (zone pellucide et/ou oelemme). Des expériences d’invalidation du gène de l′ACEt chez la souris ont montré que les mâles homozygotes ACEt−/− présentaient une faible descendanceVingt quatre patients ont été inclus dont 10 cas avec un sperme normal et un échec total de fécondation lors d’une FIV et 14 témoins ayant les mêmes caractéristiques spermatiques mais présentant de bons taux de fécondation (≥65%). L’étude de l’expression protéique de l’ACEt a été faite par western-blot sur les culots de spermatozoïdes. Un séquençage du gène codant pour l′ACEt a été fait sur l′ADN lymphocytaire.Trois cas et un témoin présentaient un défaut d’expression de l′ACEt sans diffèrence statistiquement significative entre ces deux groupes. En PCR, aucune mutation n’a été retrouvée après séquençage du gène de l′ACEt.Nos résultats n’ont pas objectivé une implication de l′ACEt dans l′interaction entre ovocyte et spermatozoïde et notamment dans la fixation à la ZP.

Initialement destinée aux problèmes tubaires, laFIV a connu une large extension de ses indications,en particulier une forte augmentation des ICSI.Sa place est variable selon le type d’indication :d’emblée, secondaire ou de dernier recours.Cet article passe en revue les indications de la FIV+/- ICSI : tubaire, endométriosique, dysovulatoire,inexpliquée (ou idiopathique), masculine et danscertains cas particuliers : préservation de la fertilité,risque viral, diagnostic pre-implantatoireLe caractère attractif de la FIV pour les couples nedoit pas faire oublier qu'il existe d’autres méthodesde traitement de l'infertilité.

Of 44 pregnancies obtained at the Tenon Maternity Hospital by in vitro fertilization (IVF) using donated oocytes, 25 have already been completed by spontaneous delivery or cesarean section: 22 (88%) single; 2 (8%) twins, and 1 (4%) triple. The most frequently seen complications of pregnancy were hypertension (16%) and preterm labor in the last 3 months (12%). However, as compared to a control group of 275 pregnancies resulting from classical IVF, the only difference was a very high percentage of cesarean sections (72%). No fetal deaths or neonatal malformations were reported.

Objective To raise the possibility that pregnancy can be obtained by assisted reproductive techniques in patients with human seminal plasma allergy. Design Case report. Setting University hospital. Patient(s) A woman consulted for a 3-year primary infertility. She reported lack of intercourse because of a seminal plasma allergy. Intervention(s) One intrauterine insemination associated with antihistamine treatment was performed with carefully washed spermatozoa. Result(s) Immediately after the insemination, the patient had an allergic reaction treated by steroids. Fortunately, this single attempt led to a successful pregnancy, and the patient gave birth to a healthy girl. Conclusion(s) Pregnancies can be obtained in patients with seminal plasma hypersensitivity by means of intrauterine insemination. However, serious complications may occur after performing intrauterine insemination, which is not a totally reliable method to prevent an allergic reaction. Thus a multidisciplinary team should follow such patients carefully and watch for the potential risks and side effects. In vitro fertilization may represent the more cautious option.

Objective To raise the possibility that a familial chromosomal translocation associated with teratozoospermia can disrupt a gene necessary for flagellum assembly. Design Case report. Setting University hospital. Patient(s) Two brothers with infertility related to anomalies of meiotic division and of the flagella assembly, presenting the same balanced 5-12 autosomal translocation. Intervention(s) Several intracytoplasmic sperm injection (ICSI) cycles in our IVF department for both couples. Main Outcome Measure(s) Sperm analysis, karyotypes, electron microscopy, and fluorescence in situ hybridization (FISH) analysis of spermatozoa performed using probes coding for chromosomes X, Y, 13, 18, and 21. Result(s) In both brothers, sperm analysis indicated a tail stump syndrome. Electron microscopy analysis displayed complex abnormalities, which were probably related to meiotic errors. The FISH analysis indicated an increase of diploid germ cells. Karyotypes of both patients revealed the same balanced chromosomal t(5;12) (p15.1; q21) translocation. Results of ICSI cycles were comparable for both couples. A twin pregnancy was achieved in one of these two couples, but a spontaneous miscarriage occurred at 10 weeks of gestation. Conclusion(s) The flagella anomalies raise the possibility that the translocation disrupts a gene necessary for the flagellum assembly, although a mutation in a gene unrelated to the chromosome breakpoints cannot be excluded.

To evaluate intra- and post-operative complications, anatomical results, quality-of-life and sexuality after bilateral sacrospinous ligament fixation (SSLF).Retrospective longitudinal study. Between March 2001 and September 2003, 51 women with stage III or IV genital prolapse underwent bilateral SSLF at the gynecology and obstetrics university department of Tenon Hospital, Paris, France. The population characteristics were as follows: mean age (+/-S.D.) was 64+/-10 years. Mean+/-SD BMI was 25+/-4 and median (range) parity was (0-12). Forty-eight (94%) women were post-menopausal, and one-third had previously undergone hysterectomy. Intra- and post-operative complications and anatomical results were recorded. Quality-of-life questionnaires (IIQ-7 and PISQ-12) and numerical analog scales were administered as well as nine questions on digestive symptoms.The overall complication rate was 17.3%, with rectal injury in one (1.9%) women. One pararectal hematoma necessitated repeat surgery. Anterior vaginal wall prolapse (Ba=-1) occurred in three women, at 10, 16 and 19 months, but did not necessitate further surgery. The global patient satisfaction rate after bilateral SSLF was 93% (47 women). Digestive symptoms were improved after bilateral SSLF. The mean pre- and post-operative scores on the IIQ-7 and PISQ-12 questionnaires were 41+/-27 and 10+/-18 (p0.0001), and 62+/-14 and 72+/-11 (p0.0001), respectively. Posterior perineorrhaphy was associated with significantly altered sexuality.These results support the feasibility of bilateral SSLF: intra- and post-operative complication rates are acceptable, quality-of-life and sexuality are improved, and bowel function is unaffected.

The microtubular meiotic spindle of most mammals, including humans, is very sensitive to cooling [Hum. Reprod. 16 (2001) 2374; Fertil. Steril. 54 (1990) 102; Fertil. Steril. 75 (2001) 769; Zygote 3 (1995) 357] and is rapidly depolymerised even after a slight reduction in temperature to 33 degrees C. Spindle disassembly is dependent on the extent of temperature decrease and its duration. After rewarming, the recovery is far from complete. Cryoprotectants themselves may alter the spindle structure, depending on the duration and temperature of exposure, the duration of recovery at 37 degrees C and the species [Hum. Reprod. Update 2 (1996) 193]. Damage to the meiotic spindle is considered to be the cause of aneuploid embryos, by inducing chromatid non-disjunction and chromosome scattering and by disturbing the sequence of events leading to the completion of meiosis and fertilisation. Nevertheless, a consensus arose from all the studies: appropriate exposure to cryoprotectants and appropriate rates of cooling and thawing allow the cryopreservation of mature oocytes without any significant changes in their second meiotic spindle organisation and without any increase in the rate of aneuploid embryos [Mol. Hum. Reprod. 2 (1996) 445; Hum. Reprod. 8 (1993) 1101; Hum. Reprod. 9 (1994) 684; Microsc. Res. Technol. 27 (1994) 165; Fertil. Steril. 75 (2001) 354]. These fundamental studies in humans, showing good preservation of cell structures after freeze-thaw procedures opened the way to new successful clinical trials with embryos derived from cryopreserved mature oocytes [Fertil. Steril. 68 (1997) 724]. Considering immature oocyte freezing at prophase I (germinal vesicle (GV) stage), a stage which was thought to be less sensitive to cryoinjury, pooled data from the literature showed no advantage in terms of survival rates, fertilisation rates of in vitro matured oocytes and developmental ability of the resulting embryos, especially in unstimulated cycles. Moreover, conflicting results are reported on the effects of freezing on the spindle-chromosome configuration of immature oocytes or in vitro matured oocytes, highlighting the need for large scale studies [Hum. Reprod. 10 (1995) 1816; Hum. Reprod. 13 (Suppl. 3) (1998) 161; Hum. Reprod. 17 (2002) 1885; Microsc. Res. Technol. 27 (1994) 165; Fertil. Steril. 68 (1997) 920]. One child has been born after the use of cryopreserved immature oocytes at GV stage, matured in vitro and fertilised by ICSI [Hum. Reprod. 13 (1998) 3156], demonstrating at least the feasibility of this technique. Improvements are required so as to make mature and immature oocyte cryopreservation an established and safe technique for ART.

Objective To determine the impact of circulating LH concentrations during controlled ovarian hyperstimulation on the outcome of IVF. Design Retrospective study. Setting University hospital. Patient(s) Two-hundred seventy women who had a short stimulation protocol with GnRH antagonist and ovarian stimulation with recombinant FSH (rFSH). Intervention(s) GnRH antagonist and rFSH were administered SC; blood samples were collected on the day of GnRH antagonist administration, 1 day after, and on the day of hCG administration. Main outcome measure(s) A threshold of 0.5 IU/L on the day of hCG was chosen to discriminate between women with LH concentrations ≤0.5 IU/L (group A, n=119) or >0.5 IU/L (group B, n=151). Result(s) The two groups were comparable with regard to the clinical parameters. In group A, significantly lower LH concentrations were observed on day 9 of the cycle and on the day of hCG administration. The numbers of oocytes retrieved, embryos obtained, and embryos cryopreserved were significantly higher in group A compared with group B. The proportion of clinical pregnancies was similar in the two groups (21.1% vs. 22.7 % per ET). Conclusion(s) In GnRH antagonist and rFSH protocols, suppressed serum LH concentrations do not have any influence on the final stages of follicular maturation, pregnancy rates, or outcomes.

The rare association of Cushing's syndrome and pregnancy is explained by the amenorrhea and sterility inherent to the syndrome. In the literature, 125 cases have been reported: 30 cases of early diagnosis and 95 others diagnosed in the second half of pregnancy.When hypercorticism exists before pregnancy it is hardly secretory. Its diagnosis, at an early stage, is not hindered by the hormone modifications of pregnancy. Its aetiological treatment raises the problem of the compatibility in pursuing the latter.The positive and aetiological diagnoses of Cushing's syndrome are difficult and its prevalence may therefore be underestimated. The evocative clinical signs are unspecific: excessive weight gain, hypertension of pregnancy and gestational diabetes. The 24-hour free hypercortisoluria and the absence of dexamethasone inhibition are of little diagnostic value after the 14th week of amenorrhea. The positive diagnosis therefore relies essentially on the abolition of the circadian rhythm of cortisol. The biological hyperandrogenia commonly observed is not discriminating. Adrenal aetiologies are frequent. Imaging must be performed to eliminate an adrenocortical tumor.The maternal prognosis depends on the hypertension, preeclampsia, diabetes and the complications of Cushing's syndrome. It depends on the activity of the hypercorticism and its early aetiological treatment, which must not be delayed after pregnancy. The foetal prognosis depends on the maternal prognosis. It is represented by preterm delivery, hypotrophy and death of the foetus in utero. The therapeutic management must be symptomatic and aetiologic, maternal and obstetrical.

Purpose: To evaluate our data concerning prognostic factors and treatment toxicity in a series of operable cervical carcinomas. Methods and Materials: Between May 1972 and January 1994, 414 patients with cervical carcinoma, staged according to the 1995 FIGO staging system (286 Stage IB1, 38 Stage IB2, 56 Stage IIA, and 34 Stage IIB with 1/3 proximal parametrial involvement), underwent radical hysterectomy with ( n = 380) or without ( n = 34) bilateral pelvic lymph node dissection (N+: n = 68). Group I included 168 patients who received postoperative radiation therapy (RT): 64 patients had low-dose-rate vaginal brachytherapy with a median total dose (MTD) of 50 Gy; 93 patients had external beam pelvic RT (EBPRT) with an MTD of 45 Gy over 5 weeks, followed by low-dose-rate vaginal brachytherapy (MTD: 20 Gy); and 11 patients had EBPRT alone (MTD: 50 Gy over 6 weeks). Group II included 246 patients treated with preoperative low-dose-rate uterovaginal brachytherapy (MTD: 65 Gy); 32 of these 246 patients also received postoperative EBPRT (MTD: 45 Gy over 5 weeks) delivered to the parametria and pelvic nodes. Mean follow-up from the beginning of treatment was 106 months. Results: First events included isolated locoregional recurrences (35 patients), isolated distant metastases (27 patients), and locoregional recurrences with synchronous metastases (13 patients). The 10-year disease-free survival (DFS) rate was 88% for Stage IB1, 44% for Stage IB2, 65% for Stage IIA, and 48% for Stage IIB. Multivariate analysis showed that independent factors influencing the probability of DFS were as follows: cervical site (exocervical or endocervical vs. both endo- and exocervical, relative risk [RR]: 1.77, p = 0.047), vascular space invasion (no vs. yes, RR: 1.95, p = 0.041), age (>51 years vs. ≤51 years, RR: 1.90, p = 0.013), 1995 FIGO staging system (IB1 vs. IIA, RR: 2.95, p = 0.004; IB1 vs. IB2, RR: 3.49, p = 0.0009; and IB1 vs. IIB, RR: 4.54, p = 0.00002), and histologic pelvic lymph node involvement (N− vs. N+, RR: 2.94, p = 0.00009). The sequence of adjuvant RT did not influence the probability of DFS (Group I vs. Group II, p = 0.10). In Group II, after univariate analysis, DFS was significantly influenced by histologic residual cervical tumor in the hysterectomy specimen (yes vs. no: 71% vs. 93%, respectively, p −6 ) and by the size of the residual tumor (≤1 cm vs. >1 cm: 83% vs. 41%, respectively, p = 0.001). The overall postoperative complication rate was 10% in Group I and 9% in Group II ( p = 0.7). The rate of postoperative ureteral complications requiring surgical intervention was lower in Group I than in Group II (0.6% vs. 2.3%, respectively, p = 0.03). The overall 10-year rate for Grade 3 and 4 late radiation complications was 10.4%. Postoperative EBPRT significantly increased the 10-year rate for Grade 3 and 4 late radiation complications (yes vs. no: 22% vs. 7%, respectively, p = 0.0002). Conclusion: The prognosis for patients with cervical carcinoma was not influenced by the sequence of adjuvant RT (preoperative uterovaginal brachytherapy vs. postoperative RT) for Stages IB, IIA, and IIB with 1/3 proximal parametrial involvement. However, postoperative EBPRT increased the risk of late radiation complications.