Apolipoproteins L1 and L3 control mitochondrial membrane dynamics.

Apolipoproteins L1 and L3 (APOLs) are associated at the Golgi with the membrane fission factors phosphatidylinositol 4-kinase-IIIB (PI4KB) and non-muscular myosin 2A. Either APOL1 C-terminal truncation (APOL1Δ) or APOL3 deletion (APOL3-KO [knockout]) reduces PI4KB activity and triggers actomyosin reorganization. We report that APOL3, but not APOL1, controls PI4KB activity through interaction with PI4KB and neuronal calcium sensor-1 or calneuron-1. Both APOLs are present in Golgi-derived autophagy-related protein 9A vesicles, which are involved in PI4KB trafficking. Like APOL3-KO, APOL1Δ induces PI4KB dissociation from APOL3, linked to reduction of mitophagy flux and production of mitochondrial reactive oxygen species. APOL1 and APOL3, respectively, can interact with the mitophagy receptor prohibitin-2 and the mitophagosome membrane fusion factor vesicle-associated membrane protein-8 (VAMP8). While APOL1 conditions PI4KB and APOL3 involvement in mitochondrion fission and mitophagy, APOL3-VAMP8 interaction promotes fusion between mitophagosomal and endolysosomal membranes. We propose that APOL3 controls mitochondrial membrane dynamics through interactions with the fission factor PI4KB and the fusion factor VAMP8.

Arginine vasopressin in human follicular fluid.

Arginine vasopressin (AVP) was determined in plasma and follicular fluid in 28 women in an in vitro fertilization program. In 23 women, follicular fluid was collected by laparoscopy during general anesthesia, and in 5 women, it was collected transvaginally with no such anesthesia. Plasma AVP increased markedly from its basal (preanesthesia) value in the first group, whereas it did not change in the second group. AVP concentrations were approximately 10-fold lower in the follicular fluid than in the plasma collected simultaneously in the anesthetized women. AVP levels were not significantly different in plasma and follicular fluid in the women of the second group. AVP concentrations were similar in ovarian venous and brachial venous plasma in 4 women during surgery. These results indicate that AVP concentrations in follicular fluid are equal to or lower than those in plasma and that AVP concentrations are not higher in efferent blood from the ovary than in peripheral blood.

A multiparametric analysis of endometrial estrogen and progesterone receptors after the postovulatory administration of mifepristone.

A double-blind randomized study was performed in two groups of eight normally cycling patients: group I received 10 mg/d of RU486 for 4 days from the date of ovulation and group II received a placebo. On day +5, cytosol and endometrial estrogen receptors (ERs), and progesterone receptors (PRs) were analyzed by radioligand binding assay as well as by enzyme immunochemistry. Histologic studies showed that all the endometria of group I were abnormal (luteal insufficiency and/or E/P imbalance). The nuclear PR levels were significantly higher in group I (843 +/- 422 fmol/mg) deoxyribonucleic (DNA) compared with 482 +/- 232 fmol/mg DNA in group II. Immunohistochemical study showed that ER and PR staining was higher for both glands and stroma in group I (52% and 72% for the respective receptors), compared with the receptor-immunostained surface observed in group II, which was reduced to 40% for ER and to 4% for PR. This study demonstrates that RU486 administered in the immediate postovulatory period blocks normal tissue evolution in the follicular phase as well as the processing of PR.

Pregnancies after replacement of frozen-thawed embryos in a donation program.

Eighteen patients with primary (n = 8) or secondary (n = 10) ovarian failure were enrolled in a donation program. In 15 cases, the oocytes were donated anonymously; in 3 cases, they were donated by the sister of the recipient. All the recipients had cyclic steroid replacement therapy that included estrogens and progesterone administered by the transdermal and tranvaginal routes, respectively. The embryos obtained were cryopreserved and replaced with no attempt at synchronization between donor and recipient. Steroid hormonal patterns were within the range for the normal menstrual cycle and endometrial biopsies taken on day 21 or 22 of the treatment cycles were independently assessed as being representative of day 21 +/- 2. Four of 12 transfers were successful (31%): 1 patient aborted at 6 weeks, and the three others were delivered, one normally and two by cesarian sections. The authors' practice suggests the following: (1) steroid supplementation by transdermal and transvaginal routes is effective, (2) synchronization between donor and recipient is no longer required with the use of frozen-thawed embryos, and (3) the "temporal window" is large since all the replacements were done on day 14 of the cycle.

Hormonal secretions in singleton pregnancies arising from the implantation of fresh or frozen embryos after oocyte donation in women with ovarian failure.

OBJECTIVE: To determine whether levels of human chorionic gonadotropin (hCG), 17 beta-estradiol (E2), and progesterone (P) are different in the peri-implantation phase of fresh versus frozen embryos. DESIGN: Hormonal secretions were measured on days 9 and 11 after implantation and at 4, 5, and 6 weeks gestation. PATIENTS: Thirty-one pregnancies were achieved in 65 patients with ovarian failure. Seventeen singleton pregnancies developed after implantation of 4 frozen and 13 fresh embryos. RESULTS: Human chorionic gonadotropin and E2, contrary to P, were higher in cases of fresh embryos from the 9th day after transfer to the 5th week at which time they become statistically significant (respectively, for hCG and E2, 5,800.3 +/- 332.3 versus 2,027.3 +/- 916.3 [mean +/- SD] mIU/mL for hCG and 562.3 +/- 215 versus 291 +/- 152 pg/mL for E2). CONCLUSIONS: This difference might be explained by either the higher number of fresh embryo replaced or by the fact that the number of blastomeres and also their metabolic activity could be reduced after freezing and thawing.

The influence of psychological factors on the outcome of the fertilization step of in vitro fertilization.

Our objective was to determine whether psychological factors have an influence on the outcome of the fertilization step of in vitro fertilization (IVF) trials. The design was a prospective cohort study. We studied 48 women and 32 of their spouses. Each subject was assessed psychologically on the day before oocyte retrieval (OR) with the Child Project Questionnaire (CPQ) and the Ways of Coping Checklist. In addition, the State-Trait Anxiety Inventory was filled in by subjects 2 days before OR, and the State form was completed again for 6 additional days. The outcome measure was the success of the fertilization step. Logistic regression analysis was used to test the influence of psychological factors while taking into account the effect of medical and sociodemographic variables. The following variables were found to be statistically significant predictors of fertilization: normal sperm; tubal lesions or occlusion; women's factor II of the CPQ, i.e. Perception of Marital Harmony in the Project to Conceive a Child. We conclude that, even when the influence of biomedical variables is taken into account, the women's Perception of Marital Harmony in the Project to Conceive a Child, is a statistically significant predictor of the success of the fertilization step of IVF.

Endoscopic SIS injection into the lower oesophageal sphincter in dogs.

AIM: To determine the usefulness of endoscopically-delivered small intestinal submucosa (SIS) as a scaffold in enhancing the lower oesophageal sphincter (LOS) pressures. METHODS: Six dogs were endoscopically injected--four with the SIS and two with its glycerin carrier. Manometry was performed prior to injection and every four weeks post-op. RESULTS: Adequate and site correct injections were made in four dogs. In one dog, significant augmentation of pressures were obtained at four weeks. None had significant changes in pressure at eight weeks, differences in length at either four or eight weeks or significant differences in the thickness of the examined layers. Four of the six had capillary cushions on pathological examination. The dog injected with the carrier had a loose and disorganise collection, while the others were well organised. CONCLUSION: SIS is a biologically compatible material. Lack of an animal model for gastro-oesophageal reflux disease (GORD) makes determining the ability of injections of SIS to combat reflux problematic.

[Therapeutic management of ovarian dystrophy and insufficiency in abortion disorders: recent data]. / Prise en charge thérapeutique de la dystrophie et de l'insuffisance ovarienne débutante dans la maladie abortive: données récentes.

Many reports suggested that the high rate of miscarriage in women with polycystic ovaries may be due to increased urine and/or plasma LH concentration. In fact, with the exception of pulsatile GnRH, any treatment likely to increase the plasma LH level results in unchanged or rather low miscarriage rates. Conversely, a reduction in this rate by GnRH agonists is not conclusive. Excess weight may also increase the risk of miscarriage. In women with incipient ovarian failure, the miscarriage rate is mainly linked to age. No stimulation has been found to be effective in these patients. There is a need for more extensive evaluation in GnRH analog microdoses, recombinant FSH and GnRH antagonists. Oocyte donations from younger women are difficult to obtain because of the lack of donors in France.

[Echographic studies of the thickness of the endometrium during spontaneous and induced cycles: its application to in-vitro fertilization]. / Etude échographique de l'épaisseur de l'endomètre au cours des cycles spontanés et stimulés: Applications à la fécondation in vitro.

The authors have estimated the thickness of the endometrium by measuring it ultrasonically between the 5th preovulatory and the 6th post-ovulatory day. This study, which was carried out as part of an in vitro fertilisation programme (IVF) was performed during 162 cycles of which 22 were spontaneous and 140 were stimulated by Clomiphene and HMG. The endometrium is significantly thicker and grows more rapidly when the cycles are stimulated. There is a correlation between the levels of progesterone in the blood and the thickness of the endometrium on the 2nd post-laparoscopy day. On the other hand there was no relationship between the thickness of the endometrium and with the development or otherwise of a pregnancy after replacing embryos.

[Extrauterine pregnancy following in vitro fertilization, 2 of these associated with a developing intrauterine pregnancy]. / Grossesses extra-utérines après fécondation in vitro, dont deux associées à une grossesse intra-utérine évolutive.

Five cases of extra-uterine pregnancy occurred after in vitro fertilisation and embryo transfer. The case histories are given. All pregnancies occurred in the ampullary portions of the tubes. In two of the cases there was an on-going intra-uterine pregnancy as well as the ectopic. After the extra-uterine pregnancy had been operated on the intra-uterine pregnancies continued normally to term. In considering the tubal physiology the authors attempt to draw conclusions about the factors causing ectopic pregnancies after in vitro fertilisation.

[Prognostic value of preovulatory elevations of plasma progesterone during in vitro fertilization using LHRH agonists in a long protocol]. / Valeur pronostique des élévations pré-ovulatoires de la progestérone plasmatique au cours des fécondations in vitro sous agonistes de la LHRH en protocole long.

We retrospectively analyzed the prevalence and prognostic significance of plasma progesterone rises during in vitro fertilization (IVF) protocols including pituitary down-regulation by LHRH agonists in a long protocol and stimulation by hMG (n = 1,116: Group A) or pure FSH (n = 178: Group B). On the day of hCG injection, plasma progesterone level was in the 0.60-0.99 ng/ml range in 7.1% of group A patients and 6.2% of group B patients (NS) and above 1 ng/ml in respectively 4.0% and 3.4% of the cases (NS). On the same day, plasma progesterone was strongly correlated with plasma estradiol (r = 0.26 - p < 0.001 in group A; r = 0.21 - p < 0.01 in group B). However, increased progesterone levels were not associated with changes in plasma LH levels, falls in plasma estradiol levels after hCG injection, or significant modifications in biological and clinical results of IVF. The cause of this pattern of progesterone rise remains to be elucidated.

[Characteristics of pregnancies obtained by in vitro fertilization]. / Caractéristiques des grossesses obtenues par fécondation in vitro.

193 patients had 212 cycles induced for in vitro fertilisation between May 1983 and May 1984. 20 pregnancies of which 10 are still in progress were obtained with 6 spontaneous abortions. There were 2 so-called biochemical pregnancies and 3 extra-uterine pregnancies. The figure of 17% pregnancies where embryos were replaced totals less than 10% if one considers those pregnancies that really carry on. The number of extra-uterine pregnancies is disturbing. Finally, 2 multiple pregnancies continued, one of them being a quadruple pregnancy. The authors have made a special study to see the parameters of the conditions under which the pregnancies were obtained and the prognosis for such pregnancies.

[Outcome beyond the 1st trimester of 305 pregnancies conceived by fertilization in vitro]. / Evolution au-delà du premier trimestre de 305 grossesses obtenues par fécondation in vitro.

The obstetrical outcome of 305 pregnancies obtained by in vitro fertilization were reviewed: out of 275 pregnancies following fresh embryo transfers, 205 (74.5%) were single, 64 (23.3%) double and 6 (2.2%) triple). We observed increased frequencies of high blood pressure linked to older maternal age, bleeding in the late pregnancy and breech presentation, which could be associated to abnormal insertion of umbilical cord and/or placenta. Multiple pregnancies, especially the triple ones, are of the highest risk (intra-uterine growth retardation, low birth weight). Nevertheless the total fetal mortality remains low in our experience. Data about 22 pregnancies following cryopreserved embryo transfer, 5 after oocyte donation and 3 therapeutic abortions are also given.

[Ovarian stimulation for in vitro fertilization using LHRH agonists: comparison of plasma and intra-follicular hormone profiles using "short" and "long" protocols]. / Stimulation ovarienne pour fécondation in vitro utilisant les agonistes de la LHRH: comparison des profils hormonaux plasmatiques et intra-folliculaires des protocoles "courts" et "longs".

Plasmatic estradiol (E2), progesterone (P) and LH were measured during the follicular phase of 343 cycles induced for in vitro fertilization (IVF) using a LHRH agonist in a "long protocol" (Group I) and 76 cycles in a "short protocol" (Group II). Moreover measurements in the plasma and follicular fluid (FF) of E2, P, LH, Delta-4-androstenedione (A), Testosterone (T) and prolactin (PRL) were performed on the day of oocyte retrieval (DO) in 46 women of the group I (111 FF) and 27 of the group II (67 FF). In the group I, plasma LH always remains below 3 mUl/ml, whatever the type of agonist (Buserelin or DTRP6-LHRH) and the type of stimulation (HMG or FSH) are used. On the other hand in the group II, mean plasma LH and P levels from D-5 to D-2 and those of FF LH, T and A on DO are significantly higher than in the group I. These changes are associated with a significant decrease of retrieved oocytes (5.8 versus 7.8 p less than 0.0001), pregnancy rate (15% versus 30%, p less than 0.01) and ongoing pregnancy rate (10% versus 22%, per oocyte retrieval, p less than 0.01). They suggest that the pituitary desensitization could be unsatisfactory with the short protocol use of agonist.

[Posterior urethral valves in the very young infant: rupture by balloon catheter]. / Valves de l'urètre postérieur du tout petit: rupture par sonde à ballonnet.

A simple treatment of valves obstructing the posterior urethra in male neonates consists of breaking them by pulling a balloon catheter. This technique is preferable to instrumental manoeuvres, always delicate in such small urethras. In the case reported here a 28-months follow-up showed satisfactory results with regard to both renal function and urinary continence.

[Immunological disorders of coagulation in habitual abortion. Prospective study]. / Désordres immunologiques de la coagulation dans la maladie abortive. Etude prospective.

The physiopathological role of antithromboplastin-type circulating anticoagulants in habitual abortion may be envisaged since the presence of antithromboplastin has been reported in most studies on women at high risk of abortion. To avoid a possible statistical bias, we conducted a prospective study in a sufficiently large group of women with habitual abortion (n = 99) compared with a control group of women with normal fecundity (n = 50). In addition, all women were investigated for lupus symptoms. The circulating antibody was detected by the diluted thromboplastin time and activated cephalin time methods. The results were considered positive when the patient/control diluted thromboplastin time ratio was 1.2 and/or when the increase in activated cephalin time was not corrected by a control plasma. In the patients' group, 10 women (10%) had an anti-thromboplastin type circulating anticoagulant, whereas no circulating anticoagulant could be detected in the control group. Three women with circulating anticoagulant had signs of systemic lupus erythematosus. None of the patients presented with Soulier-Boffa syndrome. These data have established a significant correlation between habitual abortion and circulating anticoagulant whilst avoiding statistical bias. Our results suggest that women with idiopathic habitual abortion should be subjected to systematic immunological exploration and that a small number of them should be followed attentively.

[Oocyte donation after the bioethics law. Medical, ethical and legal implications drawn form a series of 300 cases at the Tenon hospital]. / Le don d'ovocytes depuis la loi de bioéthique. Implications médicales, éthiques et juridiques déduites d'une série de 300 cas à l'hôpital Tenon.

This is the perfect example of the problems which are the consequences of the actual medicine. We carried out an ovocyte donation study at the Tenon Hospital, in Paris, between 1994 and 1999 involving 177 cryopreserved thawed embryo transfers among 300 recipients. This study enables us to stress the ethical difficulties posed by the so called bioethical laws of 1994. Simultaneously two consequences became clearly evident: a paucity of donors, and the necessity to only transfer frozen embryos due to decree of 1996 upon sanitary security that imposes the quarantine of embryos for six months. On the other hand, the use of this method has yielded important new information regarding embryo implantation and the importance of ovocyte quality that is closely correlated to donor age.

[Oocyte and embryo donations]. / Dons d'ovocytes et d'embryons.

Oocyte donation was introduced in 1983 either to treat infertility due to the absence of ovocytes (gonadal dysgenesis, premature menopause, etc.) or to avoid the risk of genetic disease transmitted by ovocytes. Practical problems have been solved by using substitutive treatments including natural steroids and by freezing embryos that are not synchronous with the recipient. However, ethical problems are more delicate and notably, they raise the issue of non-anonymous donation. A review of the literature shows that up to now 327 transfers have been performed, with a 24 p. 100 rate of maintained pregnancy.