Fertilizing ability of sperm with unexplained in vitro fertilization failures, as assessed by the zona-free hamster egg penetration assay: its prognostic value for sperm-oolemma interaction.

OBJECTIVE: To investigate the fertilizing ability of sperm with previous unexplained IVF failure using the zona-free hamster egg penetration assay. DESIGN: Three hundred ninety-six tests were performed after multiple IVF failures. In a subsequent prospective study, 38 IVF attempts using the microdrop insemination technique and 81 subzonal inseminations (SUZI) were performed. One hundred thirty-two tests with donor sperm were carried out as controls. PATIENTS: Three hundred fifty-two patients who had a minimum of two unexplained IVF failures including at least 10 metaphase II oocytes were included in the study. RESULTS: The ability of the patient sperm to bind to hamster oocytes was lower than that of controls. The largest differences were the percentage of oocytes with swollen sperm heads and the mean number of decondensed sperm heads per penetrated oocyte: both were much lower for patients than controls. Patients with a test result nil did not fertilize any oocytes during the SUZI cycles (n = 7; 50 oocytes), and the post-SUZI fertilization rate for patients with a test value < 10% was significantly lower than that of others (5.4 +/- 10.3 versus 23.8 +/- 8.4, respectively). CONCLUSIONS: The defect of sperm involved in IVF failures is mainly a reduction of their fusiogenic ability and not their ability to recognize and bind to the oolemma. Patients with a test result < 10% had a significantly reduced post-SUZI fertilization rate. A test score of zero indicates a major and permanent impairment of the sperm fusiogenic ability.

[Late cerclage]. / Le cerclage tardif.

Cervico-isthmial incompetence develops in the second trimester of pregnancy. There are problems as to the correct treatment. The authors report four cases where stitches were put in late using the technique of "parachute" cerclage. This made it possible for four live babies to be born. A search of the literature shows that after late cerclage in 60-90% of cases pregnancy continues normally. But it has to be realised that complications do occur and these are mainly chorio-amnionitis which carries a bad prognosis obstetrically and also premature rupture of the membranes. The authors recommend this manoeuvre in spite of the risks because of the benefits that can be obtained. The procedure should only be carried out if there is no cervico-vaginal infection as determined by negative swabs and tocolytic treatment should also be given.

[Megabladder. Microcolon. Prenatal ultrasonic diagnosis and a review of the literature. Apropos of a case]. / Mégavessie. Microcôlon. Diagnostic échographique anténatal et revue de la littérature. A propos d'un cas.

The condition of "megacystis-microcolon" is a very rare condition which can now be diagnosed ante-natally due to ultrasound. The presence of a megacystis (large bladder) with increased levels of amniotic fluid makes it possible to eliminate other ante-natal causes of dilatation of the bladder and in particular when it is found in a female fetus (as it is in 80% of cases). At birth, one finds, apart from the massive dilatation of the bladder with very little effect on the upper urinary tract, a microcolon with complete absence of peristalsis. This last abnormality always leads to a catastrophic short term result because treatment is quite ineffective. Many histological studies have been carried out and these sometimes differ from one another but it is possible to think that the condition is due to pathology of neurogenic origin in the muscle of the bladder and the aetiology of this is unknown. Finally, because there have been a few familial cases, there may be a genetic element in this illness that has such a poor prognosis.

[Drug surveillance and reproduction: the bad example of distilbene]. / Pharmacovigilance et reproduction: le mauvais exemple du Distilbène.

In the 1940's, diethylstilboestrol (DES) is one of the first hormonal therapeutics which was prescribed to many pregnant women by a lot of gynecologists. Until 1970, the indications of this therapy was enlarged, before carcinologic and reproductive consequences leaded to forbid obstetrical indications of DES (in France, in 1977 only). In France, 80,000 girls and 80,000 boys are suspected to have been exposed. As far as girls are concerned, the studies estimate between 23% and 36% the rate of infertility. These studies show also an increased incidence of ectopic pregnancy, spontaneous abortions, and premature delivery. The association between various factors of infertility, and typical uterine abnormalities leads to specific therapeutical indications, mostly in assisted procreations. The history of DES points out prescriptions of a therapeutic without proofs of its efficiency, the silence of pharmaceutical laboratories which did not take into consideration Dieckman's evaluation, and the difficulties for physicians in affording information. Nevertheless, the last patients exposed will be 40 years old in 2016 in France. The other hormonal therapeutics which were discovered gave in turn rise hope for enhancing the fertility and providing from miscarriage. Over the examples such as DES are not still resolved questions that patients and physicians ask concerning the lack of adverse effects of a therapy on the foetus, when its clinical efficiency on the pregnancy is supposed to be proved.

Human oocyte cytometry and fertilisation rate after subzonal insemination.

The cytometry of 545 oocytes was evaluated during subzonal insemination (SUZI; 85 attempts), on day 0 (egg retrieval and SUZI), day 1 and day 2 (embryo transfer). On day 0, the egg and oolemma diameters (mean +/- SD) were 164.0 +/- 19.6 microns and 114.2 +/- 16.8 mu 5m respectively. The zona thickness was 17.8 +/- 13.4 microns and correlated with the oolemma diameter (r = 0.24, p < 0.001). The fertilisation rate was significantly lower for the smaller oocytes (less than 108 microns diameter) compared with the larger oocytes (over 108 microns) (9.8% vs 21.2% respectively; p < 0.05). There was little variation in oocyte diameter according to nuclear status. However, oocyte diameter increased significantly between day 0 and day 1 (p < 0.001) for both fertilised and unfertilised oocytes. Six different indications for SUZI were investigated in detail: three with non-specific (normal and subnormal sperm with in vitro fertilization failure, oligoasthenospermia) and three with specific sperm defects (flagellar dyskinesia, absence of outer dynein arms, antisperm antibodies). Oocytes from the non-specific defect groups had significantly smaller diameters than the others (p < 0.05). The mean fertilisation rate was related to the mean oolemma diameter for the groups with non-specific sperm defects and the group lacking dynein arms (LODA) (r = 0.91, p < 0.05). Eggs from the groups of patients with LODA and those with antisperm antibodies had thicker zona pellucida than others (p < 0.05). These findings suggest that in addition to nuclear criteria of maturity, the growth of oocytes is an important factor for fertilising ability.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential step-up and step-down dose regimen: an alternative method for ovulation induction with follicle-stimulating hormone in polycystic ovarian syndrome.

This study was designed to compare both the effectiveness and safety of two low-dose gonadotrophin regimens (step-up versus sequential step-up and step-down) for ovulation induction in polycystic ovarian syndrome (PCOS) patients. In all, 56 infertile clomiphene citrate-resistant PCOS patients were included in this prospective randomized study. A total of 38 cycles were conducted with a classic step-up protocol, whereas for 35 cycles the follicle-stimulating hormone (FSH) threshold dose was reduced by half when the leading follicle reached 14 mm in diameter (sequential protocol). Serum oestradiol, progesterone and luteinizing hormone concentrations and follicular growth rate were evaluated during the cycle. At the time of human chorionic gonadotrophin administration, cycles treated with sequential protocol exhibited significantly lower oestradiol concentrations [434 +/- 45 versus 593 +/- 67 pg/ml (mean +/- SEM)] and the number of medium-sized (14-15 mm) follicles was significantly reduced (0.3 +/- 0.1 versus 0.8 +/- 0.2) compared with cycles treated with the classic step-up protocol. Moreover, in these cycles serum luteal oestradiol concentrations were decreased significantly (350 +/- 77 versus 657 +/- 104 pg/ ml) compared with the classic step-up protocol. A sequential step-up and step-down protocol seems to be a safe and effective regimen for ovulation induction in PCOS patients. Decreasing the FSH dose following step-up follicular selection may be an alternative method to avoid multifollicular development.

[Evaluation of ovarian sensitivity to gonadotrophins: role of ovarian reserve tests]. / Evaluation de la sensibilité ovarienne aux gonadotrophines: place des tests de réserve ovarienne.

Among several parameters involved in the age-dependent reduction in conception rate, intra-ovarian factors, specially the follicular oocyte complex, play a major role. The aim of endocrine challenge tests is to assess ovarian follicular reserve. Basal serum FSH determination on day 3 of the cycle is easily measurable, inexpensive. Its sensitivity is increased with a clomiphene citrate challenge test. Both GnRH agonist stimulation test and exogenous FSH test allow to evaluate more directly the ovarian function. However they are more invasive, expensive and need further standardisation.

The hormonal flare-up following gonadotrophin-releasing hormone agonist administration is influenced by a progestogen pretreatment.

In a short-term protocol, the influence of progestogen pretreatment upon the oestradiol flare-up (delta E2) induced by gonadotrophin-releasing hormone agonist (GnRHa) was assessed in relation to in-vitro fertilization (IVF) outcome in 90 cycles programmed (n = 52) or not (n = 38) by norethisterone (10 mg/day for 12-20 days). Patients pretreated by progestogen had a significantly lower delta E2 value than patients without pretreatment (delta E2 = 26 +/- 5 versus 61 +/- 8 pg/ml, P = 0.003). It could be related to a lower gonadotrophic response for luteinizing hormone (LH) (delta LH = 9 +/- 0.8 versus 14.5 +/- 2.2 IU/l, P = 0.01). The IVF outcome (final oestradiol, number of oocytes or embryos) was similar in both groups and delta E2 was well correlated with these final parameters in each group. A significant rise in serum progesterone was observed only in patients without pretreatment (delta P = 1.1 +/- 0.2 versus 0.1 +/- 0.1 ng/ml, P < 0.0001). Thus norethisterone pretreatment decreases the oestradiol flare-up and prevents the early increase of progesterone (by avoiding some rescue of the corpus luteum or some luteinization of small developing follicles) but does not influence the outcome of the IVF cycle. In clinical practice, evaluation of the hormonal flare-up for predicting IVF outcome must take into account any pretreatment prescription.

[Physiology of human gamete interaction]. / Physiologie de l'interaction gamétique dans l'espèce humaine.

Subzonal insemination was the first micromanipulation technique used in the treatment of male factor sterility. Analysis of the sperm pathology prior to patient inclusion in the program allowed us to study gamete interaction in the human and the early embryogenesis. A series of 523 cycles and 3,027 micro-injected oocytes is reported.

Efectos de la pentoxifilina sobre la movilidad espermática en pacientes normo y oligoastenospérnicos y su relación con la fecundación in vitro

Objetivo: Determinar los efectos de la incubación de espermatozoides (spz) con Pentoxifilina (PF) sobre las características de movimiento de pacientes normo y oligoastenospérmicos y el resultado de su utilización en la fecundación in vitro (FIV) por oligoastenospermia severa. Material y Métodos: Sobre un total de 46 pacientes divididos en tres grupos: Grupo I(n=10) normospérmicos; Grupo 2a(n=14) oligoastenospermia moderada y Grupo 2b(n=22) oligoastenospermia severa se cuantificaron los parámetros de movimiento usando computer-assited sperm analysis (CASA). Una segunda parte del estudio consistió en la evaluación del resultado de fecundación in vitro(FIV) en 16 parejas del grupo 2b. Los resultados de FIV e inseminación subzonal (SUZI) con o sin PF fueron comparados. Preparación del Semen: El semen fue preparado con gradiente de percoll y dividido en dos partes, uno como control y la otra mitad fue incubada con pentoxifilina 1 mg/ml después de dos horas de capacitación. Luego de remover la PF del semen, fue analizado con CASA y tres horas después. Resultados: Se encontró un incremento significativo del desplazamiento lateral de la cabeza (ALH) solamente en el grupo 2b después de la utilización de la PF (Pmenor 0.05). En los otros dos grupos ningún efecto superior significativo de los parámetros de movimiento fue observado en comparación a una preparación solamente de percoll. Ningún aumento de la taza de fecundación fue observada cuando el semen tratado con PF fue usado comparado con el semen control. Conclusiones: Aunque la pentoxifilina puede mejorar los parámetros de movimiento en algunos pacientes con oligoastenospermia, dicho tratamiento no supera la capacidad fecundante cuando el semen ha sido previamente seleccionado con gradiente de percoll. Su utilidad en FIV por infertilidad masculina deberá ser evaluada en un grupo más amplio