Search

The aim of this study was, firstly, to define the different patterns of early cleavage (EC) observed at 26 h after either IVF or intracytoplasmic sperm injection (ICSI) and, secondly, to assess the predictive value of one of these patterns, even EC (EEC), on pregnancy rate in combination with day 2 embryo score. In the first part of the study, the relationship between three different EC patterns (EEC, uneven EC and EC with fragmentation of the day 2 embryo) and embryo morphology was determined. EEC was shown to be strongly associated with good embryo morphology. In the second part of the study, it was shown that EEC used in combination with embryo score improved selection of embryos for transfer. The presence of EEC significantly (P < 0.001) enhanced mean implantation rate in all transfer categories involving identically scored embryos, in both compulsory single embryo transfers and elective single embryo transfers. Multivariate analysis demonstrated that EEC and embryo score had strong complementary predictive value for pregnancy. Based on these findings, it was concluded that even though they are associated, EEC and embryo score could be combined to increase pregnancy rate, especially in elective single embryo transfer programmes.

The value of early cleavage (EC) assessment is still being debated. The aim of this prospective study was to examine the predictive value of EC assessment performed exactly 26 h after insemination by IVF or intracytoplasmic sperm injection (ICSI) in a programme of elective single embryo transfer (SET) performed at day 2. If day 2 scoring demonstrated several embryos with high implantation potential, an EC embryo was transferred preferentially. EC was assessed only during normal laboratory hours so that there were two groups: EC assessed, and EC not assessed, the latter being the control. A total of 277 elective SET were performed in women under 37 years undergoing their first IVF or ICSI cycle (mean age 30.5 years, range 21-37). The overall clinical and ongoing pregnancy rates were 40.1% (111/277) and 32.9% (91/277) respectively. Significantly higher overall clinical and ongoing pregnancy rates were obtained after transfer of an EC embryo than a non-EC embryo: 49.4 versus 33.3% (P < 0.05) and 42.4 versus 25.9% (P < 0.02) respectively. However there was no significant difference between the EC assessed and control groups: 40.4 versus 39.3% and 33.2 versus 32.1 respectively. These findings confirm the value of EC assessment for selection of embryos with high implantation potential.

Multiple embryo transfer is associated with a high frequency of twin pregnancies with costly complications involving both mother and child. As a result high priority is currently being given to the development of single embryo transfer (SET) programs. France seems to be lagging behind Northern European countries in the development of SET and widespread use of SET will depend on convincing physicians that this policy will not have a negative impact on success rate, as has been the case for many protocols described in the literature as well as in our own experience. Our SET program includes patients less than 36 years of age undergoing their first FIV-ICSI. If two embryos showing satisfactory morphology are obtained, one is selected transferred and the other is systematically frozen. Selection for transfer is based on two criteria, i.e. observation of even early cleavage 26 hours after FIV-ICSI and evaluation of embryo morphology score on day 2. Embryo morphology score is based on the presence of four blastomeres and absence of blastomere irregularities and anucleated fragmentation. Last, a prerequisite for SET is an effective freezing program. A pregnancy rate of 13% per thawing was sufficient enough to obtain a cumulative pregnancy rate after SET (N = 205) and subsequent frozen embryo transfer (FET) similar to the cumulative pregnancy rate obtained after double embryo transfer (N = 394) and subsequent FET (46.3 vs 46.7%, NS). Twin delivery rate were respectively 2,6% after SET and 26,6% after double embryo transfer (P < 0.01).

Objective: Prevention of twin pregnancies using elective Single Embryo Transfer (e-SET) is now considered by many Assisted Reproductive Techniques teams as a necessity. The aim of this study was to assess the efficacy of e-SET in a prospective manner in a selective population of patients using Take Home Baby Rate per couple as principal parameter., Patients and Methods: This prospective study was conducted from January 2003 to December 2004. Elective Single Embryo was proposed to women above 37 years in their first IVF or ICSI attempt. It was then performed only in cases when at least one embryo with high implantation potential (score-4 embryo in our embryo scoring) was obtained for transfer and one more (score-3 or score-4 embryo) was available for freezing., Results: e-SET was proposed and accepted in 225 couples (25% of eligible couples and 7.8% of total population) and was possible in 96 of these). Two embryos were transferred in all other eligible patients (Double Embryo Transfer group=DET). Cumulative delivery rate after fresh embryo transfers and, if necessary, after frozen-thawed embryo transfers were 39.5% per couple e-SET group and 41.7% in DET group (NS). On the other hand, the percentage of twin pregnancies was significantly different between the two groups (2.6% vs 26.6% respectively; P<0.01)., Discussion and Conclusion: In women younger than 37 years in their first IVF/ICSI attempt, the elective transfer of only one embryo with high implantation potential strongly allowed to avoid twin pregnancies without any significant delivery rate decrease. This transfer policy is particularly efficient in laboratories displaying good results in their embryo freezing program.

Background: This study was designed to assess whether the use of ganirelix in women undergoing stimulated IUI could prevent the occurrence of premature LH rises and luteinization (LH+progesterone rises)., Methods: Women of infertile couples, diagnosed with unexplained or male factor infertility, were randomized to receive either ganirelix (n=103) or placebo (n=100) in a double-blind design. All women were treated with an individualized, low-dose rFSH regimen started on day 2-3 of cycle. Ganirelix (0.25 mg/day) was started if one or more follicles>or=14 mm were visualized. Ovulation was triggered by HCG injection when at least one follicle>or=18 mm was observed and a single IUI was performed 34-42 h later. The primary efficacy outcome was the incidence of premature LH rises (+/-progesterone rise)., Results: In the ganirelix group, four subjects had a premature LH rise (value>or=10 IU/l), one LH rise prior to the start of ganirelix and three LH rises during ganirelix treatment, whereas in the placebo group 28 subjects had a premature LH rise, six subjects prior to the start of placebo and 22 subjects during placebo treatment. The incidence of LH rises was significantly lower in ganirelix cycles compared to placebo cycles (3.9 versus 28.0%; P=0.003 for ITT analysis). When excluding subjects with an LH value>or=10 IU/l before the start of ganirelix/placebo the incidence of LH rises was also significantly lower in ganirelix cycles compared to placebo cycles (2.9 versus 23.4%; P=0.003 for ITT analysis). Premature luteinization (LH rise with concomitant progesterone rise>or=1 ng/ml) was observed in one subject in the ganirelix group and in 17 subjects in the placebo group of which three subjects had a premature spontaneous ovulation. Ongoing pregnancy rates per attempt were 12.6 and 12.0% for the ganirelix and placebo groups respectively., Conclusions: Treatment with ganirelix effectively prevents premature LH rises, luteinization in subjects undergoing stimulated IUI. Low-dose rFSH regimen combined with a GnRH antagonist may be an alternative treatment option for subjects with previous proven luteinization or in subjects who would otherwise require insemination when staff are not working.

Objective: The risk of hepatitis C virus (HCV) transmission in medically assisted procreation (MAP) is debated and some researchers have proposed to exclude MAP for HCV-positive infertile patients. The objectives of this study were to assess the presence of viral RNA in the final preparation of density gradient semen fractions collected from men with chronic HCV and HIV co-infection participating in a MAP program, and to assess whether HIV co-infection influences the rate of the presence of HCV RNA in the semen., Design and Methods: The study was based on a cohort of 170 HCV-infected male patients (93 HIV co-infected) participating in a MAP program in a French center. Semen samples were subjected to standard MAP sperm preparation, using density-gradient centrifugation with 40 and 90% layers. All aliquots were tested with a commercially available HCV RNA assay (Roche Monitor), adapted for use with semen after a nucleic HCV RNA extraction modification (Organon Technika)., Results: Seminal plasma samples from 19 (11%) patients were HCV RNA positive. The positive HCV viral load in semen was less than 600 IU/ml. None of the 90% fractions from HCV-infected patients were HCV RNA positive. Among the 93 co-infected patients, 10 were positive for HCV RNA in semen and three were HIV/HCV RNA positive in semen., Conclusions: Although HCV RNA was found in the semen of 11% of patients, no purified sperm fraction, or spermatozoa used in MAP were HCV RNA positive. The 90% purified sperm fraction discards the virus and must be used with care in MAP.

A significant transient increase in laser Doppler flowmetry (LDF) signals is observed in response to a local and progressive cutaneous pressure application on healthy subjects. This reflex may be impaired in diabetic patients. The work presents a comparison between two signal processing methods that provide a clarification of this phenomenon. Analyses by the scalogram and the Hilbert-Huang transform (HHT) of LDF signals recorded at rest and during a local and progressive cutaneous pressure application are performed on healthy and type 1 diabetic subjects. Three frequency bands, corresponding to myogenic, neurogenic and endothelial related metabolic activities, are studied at different time intervals in order to take into account the dynamics of the phenomenon. The results show that both the scalogram and the HHT methods lead to the same conclusions concerning the comparisons of the myogenic, neurogenic and endothelial related metabolic activities-during the progressive pressure and at rest-in healthy and diabetic subjects. However, the HHT shows more details that may be obscured by the scalogram. Indeed, the non-locally adaptative limitations of the scalogram can remove some definition from the data. These results may improve knowledge on the above-mentioned reflex as well as on non-stationary biomedical signal processing methods.

Background: Since 2001, French law has permitted the use of assisted reproductive technology in human immunodeficiency virus (HIV)-1 infected women under strict conditions. This report describes a preliminary series of seropositive women who underwent assisted reproduction treatment at our facility. To minimize contamination of culture media, equipment, and therefore of male gametes and embryos, we chose to perform ICSI in all cases. The outcome of ICSI was compared with the outcome in an age-matched group of non-HIV-1-infected women. Since several previous reports have indicated that HIV infection may be associated with a decrease in spontaneous fertility, our goal was also to assess the fertility status of the HIV-1-infected women entering our ICSI programme., Methods: The French law governing the use of assisted reproduction protocols in HIV-1-infected women was strictly applied. The inclusion criteria were absence of ongoing disease, CD4((+)) count >200 cells/mm(3), and stable HIV-1 RNA level. Since mean age at the time of ICSI was higher in HIV-1-infected women than in the overall group of non-HIV-infected women, we compared outcome data in HIV-1-infected women (group I) to a group of non-HIV-1-infected women matched with regard to age and follicle retrieval period (group II) as well as to the overall group of women who underwent ICSI at our institution (group III)., Results: A total of 66 ovarian stimulations was performed in 29 HIV-1-infected-infected women. The percentage of cancelled cycles was higher in infected women than in matched controls (15.2 versus 4.9%, P < 0.05). The duration of ovarian stimulation (13.3 versus 11.7 days, P < 0.05) and amount of recombinant FSH injected (2898 versus 2429 IU, P < 0.001) were also higher in infected women. The number of retrieved oocytes, mature oocytes, and embryos obtained as well as embryo quality was similar in all groups. The fertilization rate was higher in infected women than in matched controls (67 versus 60%, P < 0.01). The pregnancy rate was not significantly different between groups I and II (16.1 versus 19.6%) in spite of the fact that the number of embryos transferred was purposefully restricted in the HIV-1-infected group to minimize multiple pregnancy (2.0 versus 2.4, not significant)., Conclusion: The results of this preliminary series of ICSI cycles in HIV-1-infected women indicate that optimal ovarian stimulation is slightly more difficult to achieve than in matched seronegative women. However, when criteria for oocyte retrieval were fulfilled, ICSI results were similar to those of age-matched controls.

This prospective study evaluated the crude cumulative delivery rate following delayed intracytoplasmic sperm injection (ICSI) using spermatozoa recovered by testicular extraction (TESE) and intentionally frozen in men with non-obstructive azoospermia (NOA). This procedure can be termed 'cryoTESE-ICSI'. This study involved a series of 118 patients who underwent testicular biopsy for diagnosis of NOA in the period from January 1998 to December 2002. Testicular histology confirmed the diagnosis of NOA. Testicular parenchyma was obtained surgically from both testicles under general anaesthesia. Cryopreservation of spermatozoa was performed in 51 of 118 patients (43%). Ninety-nine delayed ICSI procedures were performed. Frozen-thawed suspensions were used in all cycles. Application of pentoxifylline was required to stimulate spermatozoa in 52% of cases. Fertilization, embryo transfer, and ongoing pregnancy rates were 60, 98 and 29% respectively. The crude cumulative delivery rate was 49% after two cycles and 57% after four cycles. A total of 39 healthy children were born in 29 deliveries. Thus, cryoTESE-ICSI is an effective procedure for routine use in patients with NOA. The main advantages of cryoTESE-ICSI are to (i) avoid repeated surgical biopsy, (ii) ensure the availability of spermatozoa when the ovarian stimulation cycle is begun, and (iii) allow programmed biopsy and therefore dissociate it from ICSI.

The objective of this study was to compare, in a centre with previous experience of gonadotrophin-releasing hormone (GnRH) antagonist use, single administration of a GnRH antagonist [cetrorelix (Cetrotide) 3 mg] with a single administration of a GnRH agonist [Decapeptyl Retard 3.75 mg] in patients undergoing assisted reproduction treatment (n = 307 and 364 respectively). GnRH agonist was administered on the first day of menses, while cetrorelix was administered when the largest follicle reached 14 mm. Ovarian stimulation was performed with recombinant human FSH (r-hFSH; 150-225 IU/day). Human chorionic gonadotrophin (HCG, 10,000 IU) was administered when at least two follicles reached a mean diameter > or =18 mm. Over 90% of patients in both groups reached the criteria for HCG administration and underwent oocyte retrieval and embryo transfer. Duration of FSH therapy (9.95 versus 11.25 days) and cumulative dose of r-hFSH (1604 versus 1980 IU) were significantly reduced (P < 0.01) in the cetrorelix 3 mg group. The number of oocytes retrieved was lower (8.5 versus 11.2; P < 0.01) with cetrorelix, but the number of embryos replaced was similar (2.2 versus 2.3; NS). The pregnancy rates per oocyte retrieval were the same, 24.5%, in the antagonist and agonist groups. This study indicates that although fewer oocytes are recovered, similar pregnancy rates can be achieved with a GnRH antagonist compared with a GnRH agonist. Additionally, a single dose of 3 mg cetrorelix was administered in 84% of patients, thus being simpler and more convenient for patients. Cetrorelix 3 mg may thus be proposed as a first choice for preventing both a premature LH surge and detrimental rises in LH during ovarian stimulation prior to assisted reproduction treatment.

Background: Sebaceous carcinomas are relatively rare cutaneous tumors; there are fewer than 600 cases reported. They most commonly arise within the meibomian gland of the eyelid; fewer than 150 of the reported cases were extraocular. These tumors have a high incidence of local recurrence and regional metastasis. The relationship of sebaceous tumors and visceral malignancy is well established in the literature., Objective: We describe a 44-year-old white female with chronic progressive multiple sclerosis who developed multiple scalp sebaceous adenomas and a solitary sebaceous carcinoma., Conclusion: Extraocular sebaceous carcinomas are rare tumors with high incidence of local recurrence and regional metastasis. Surgery with wide surgical margins is the standard treatment. We report the first case of multiple sebaceous tumors in a patient with multiple sclerosis. The presence of sebaceous tumors warrants a search for an internal malignancy. Literature on sebaceous tumors and their relationship with visceral malignancies and immunologic disorders is discussed. Literature on sebaceous carcinoma with special attention to extraocular sebaceous carcinoma is also discussed.

Objective: To compare the value of 17 IVF variables, including a new mean score of transferred embryos (MSTE), in predicting pregnancy rate., Design: Retrospective study., Setting: Private IVF unit., Patient(s): Women who underwent 10,000 embryo transfers., Main Outcome Measure(s): Duration of infertility, type of infertility, female age, rank of IVF attempt, type of ovarian treatment, progesterone level, sperm count, sperm motility, sperm morphology, number of retrieved oocytes, number of mature oocytes, maturation rate, number of embryos obtained, fertilization rate, number of transferred embryos, cumulative embryo score (CES), mean score of transferred embryos (MSTE), and pregnancy rate., Result(s): Outcome of IVF-ET was significantly correlated with female age, type of infertility, number of retrieved oocytes, number of mature oocytes, maturation rate, embryos obtained, fertilization rate, transferred embryos, CES, and MSTE. Multivariate analysis demonstrated that MSTE was a better predictor of pregnancy than the number of transferred embryos and female age., Conclusion(s): Embryo quality is the best predictor of pregnancy. The embryo score described herein should be used in IVF-ET programs to choose the best embryos for transfer.

Purpose: Pentoxifylline (PF) has been used to enhance sperm motility in many in vitro fertilization programs. The twofold purpose of this study was to determine whether PF stimulates fresh or frozen epididymal and testicular totally immotile spermatozoa and whether it can be used to select viable spermatozoa for intracytoplasmic sperm injection (ICSI)., Methods: To test the effect of PF on motility, 10 samples of totally immotile spermatozoa were incubated for 10 min with 3.6 mM PF. Motility was initiated in all cases (14.8% mean motility after PF treatment of five samples of fresh or frozen epididymal spermatozoa and 13.6% mean motility of five samples of fresh or frozen testicular spermatozoa). To assess PF for selection of viable spermatozoa before ICSI, we compared the outcome of ICSI in 20 cycles using fresh or frozen epididymal or testicular PF-treated immotile spermatozoa and 139 control ICSI using fresh or frozen epididymal or testicular spontaneously motile spermatozoa., Results: Fertilization rates were similar in the PF and control groups (45.2% vs. 51.0%). Embryo quality and division stages at the time of transfer were comparable. Six pregnancies occurred in PF-ICSI group (30.0% per cycle vs. 26.6% in control group) including two deliveries of healthy children and four ongoing pregnancies.

Knowledge of the path of a bullet and how it terminates is critical for expeditious assessment and optimal management of patients with gunshot wounds. To assess the accuracy of physical examination and X-rays in these patients, a prospective study was undertaken for all gunshot victims seen for a 1-year period on a single trauma service. The paramedics and trauma surgeons' physical examinations were evaluated for whether a bullet tract could be accurately categorized as 1) through and through, 2) graze, 3) palpable under dermis, or 4) retained (ie, not palpable). The impact of X-rays was assessed with regard to how it affected the trauma surgeons' categorization. A total of 78 patients were seen with a total of 120 bullet tracts. Seventy-seven per cent were injured by assault, and 64 per cent were shot with a 9-mm or .38-caliber handgun. Twenty of 60 (33%) bullet tracts on the torso terminated with a missile that was palpable under dermis, but only 2 of 10 neck (20%), 1 of 28 extremity (4%), and 1 of 22 head/face (5%) did so. Paramedics evaluated 15 torso bullet tracts that ended palpable under dermis, of which they detected 5 (33%). Upon initial examination, the trauma surgeon detected 11 of 20 torso bullet tracts that ended palpable under dermis (55%), and detected 14 of the 20 after X-rays were done (70%). Overall, obtaining X-rays changed the categorization for 15 of 111 bullet tracts (13%). We conclude that bullet tracts on the torso result in a subcutaneously palpable bullet one-third of the time, much more frequently than in other body regions. Paramedics only detect one-third of subcutaneously palpable missiles on the torso. X-rays change the categorization of bullet tracts infrequently. We recommend that a careful examination of the skin of the torso to detect palpable missiles be incorporated into the secondary survey of patients with wounds to that body region.

A prospective, randomized, double-blind, multicentre (n = 6) study was conducted to compare the influence of either a 150 or 250 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH, Puregon) on the number of oocytes retrieved and the total dose used in down-regulated women between 30 and 39 years of age undergoing ovarian stimulation. In all, 138 women were treated with recombinant FSH, 67 with 150 IU and 71 with 250 IU. The number of oocytes retrieved in the low-dose group was 9.1 compared to 10.6 in the high-dose group (not significant). In the 30-33 years of age class receiving the 250 IU dose, a surplus of 4.2 oocytes (14.8 versus 10.6) was found, whereas in the 37-39 age class nearly one oocyte more was retrieved in the 150 IU group (8.1 versus 7.4). The total dose used to reach the criterion for human chorionic gonadotrophin (HCG) administration was 1727 IU for the women treated with 150 IU daily and 2701 IU for the 250 IU treated women (P < 0. 001). No significant relationships were found between serum FSH concentrations as obtained in the early follicular phase and the number of oocytes collected, or the total dose. It is concluded that in women between 30 and 39 years of age, the decline in number of oocytes retrieved with increasing age cannot be overcome by augmenting the daily dose of recombinant FSH from 150 to 250 IU.

The purpose of this study was to retrospectively compare the overall results and embryo quality in 102 cycles of in-vitro fertilization (IVF)-embryo transfer using normal frozen donor semen (group D) and 94 cycles of IVF-embryo transfer using husbands' teratozoospermic sperm (group T). Donor semen was purchased from men with proven fertility and normal semen parameters. Teratozoospermia was defined in group T as the presence of <20% of normal spermatozoa in semen on the day of oocyte retrieval. Exclusion criteria were a sperm count <10 x 10(6)/ml or with <10% progressive motility. Fertilization rate, transfer rate and number of transferred embryos per cycle were significantly lower in the teratozoospermic group (45 vs 72%, 66 vs 96%, 1.7 vs 2.9%, respectively). Pregnancy rate per cycle was also lower, but not significantly (18 vs 28%). However, pregnancy rate per transfer, implantation rate per transferred embryo and take home baby rate were comparable (27 vs 30%, 15 vs 15%, 21 vs 24%, respectively). Similarly, embryo quality in terms of number of embryos displaying fragmentations or irregular cells, cleavage stages and embryo scores were comparable. When group T was divided into two subgroups according to sperm count (group T1: sperm count = 10-20 x 10(6)/ml; group T2: sperm count >20 x 10(6)/ml), there was no difference between them with regard to fertilization rate, pregnancy rate or embryo quality. This study confirms low pregnancy rate per cycle in IVF-embryo transfer using teratozoospermic semen, but demonstrates for the first time that embryo quality and viability are not impaired. It is proposed that the poor pregnancy rate per cycle obtained is due only to the poor fertilization rate, and to the subsequent limited choice of embryos to be transferred.

The prognostic value of the score of embryo transfer (SET) was assessed on 1079 embryo transfers in a homogene population of patients. The SET is obtained adding the embryo score (ES) of each transferred embryos. ES is based both on the conventional parameters of embryo morphology, and on the 4-cell stage which is the optimum division stage regarding implantation. The SET is strongly correlated with the pregnancy rate (p < 10-5), and is, with the mean score of transferred embryos (MSTE), the most sensitive and specific parameter of all studied parameters. However, embryo quality seems not to be correlated with miscarriages.

The purpose of this study was to devise an embryo score to predict the likelihood of successful implantation after in-vitro fertilization (IVF). Unlike most studies dealing with the influence of embryo stage and morphology on pregnancy, our study was based on single rather than multiple embryo transfers. A total of 957 single embryo transfers were carried out. No delivery was obtained after any of the 99 transfers using 1-cell embryos or embryos obtained after delayed fertilization. In the remaining 858 transfers, the embryos had cleaved. Higher pregnancy rates were obtained with embryos displaying no irregular cells (11.7 versus 6.9%; P < 0.01) and embryos displaying no fragmentation (11.5 versus 8.1%; P < 0.05). The 4-cell embryos implanted 2-fold more often than embryos with more or less cells (15.6 versus 7.4%; P < 0.01). Based on these observations, we devised a 4-point embryo score in which embryos are assigned 1 point each if they (i) are cleaved, (ii) present no fragmentation, (iii) display no irregularities, and (iv) have four cells. Both pregnancy rate and take home baby rate were significantly correlated with embryo score. Each point of this score corresponds to a 4% increase in pregnancy rate. Interestingly, pregnancy rate was significantly lower in women aged > 38 years (8.2 versus 11.4%; P < 0.05), even though embryo quality was similar regardless of age. Single embryo transfer allowed us to define a simple and useful embryo score to choose the best embryo for transfer to optimize IVF and embryo transfer outcome. The use of this embryo score could decrease multiple pregnancies after multiple embryo transfers.

We report here the results of a study comparing the quality of the embryos obtained after conventional IVF and after ICSI (respectively 872 and 459 embryos for 184 and 108 cycles). In the ICSI group, the female age was lower than in the IVF group, the oestradiol level on the day of hCG injection was higher, so that the number of retrieved oocytes and the number of mature oocytes. The policy of transfer being the same in the two groups, the mean number of transferred embryos was identical. The percentage of embryos without anucleate fragments, the percentage of embryos without irregularities, the percentage of 1, 2, 3, 4 or 5-cell embryos and the distribution of embryos in the 5 embryo scores were similar. In both IVF and ICSI groups, the transfer score (sum of the embryo scores of each transferred embryo) was higher for the patients who achieved pregnancy.

The purpose of this study was to compare visual and computerized assisted semen analysis (CASA) in an in vitro fertilization program. Both methods were performed on the day of 316 oocyte retrievals. CASA was performed using a Hamilton 7.2 device adjusted in accordance with the settings defined by a group of 14 French centers. Despite a few discrepancies, the correlation between visual and CASA sperm counts was significant (p < 0.001), so that between the two total motility assessments. The same correlation (Pearson's test) was observed between the fertilization rate and the parameters obtained by visual analysis and CASA. VAP, VSL, VCL and ALH exhibited threshold values under which the mean fertilization rate was below 50%. This study demonstrates the satisfactory reliability of CASA although it cannot yet replace visual analysis.

Objective: To assess the value of subzonal insemination (SUZI) in cases of total or extreme asthenozoospermia., Design: The results of IVF after SUZI were assessed in six cycles (four couples) with documented asthenozoospermia., Setting: Institut de Médecine de la Reproduction, Marseille, France., Patients: Four couples underwent six retrieval cycles. In all cases asthenozoospermia was total (100% of immotile spermatozoa) or extreme (5% nonprogressive motility). Oligozoospermia and teratozoospermia were ruled out in all cases. In two cases electron microscopy revealed the absence of the central singlet in the flagellum axonemal complex and in one case a major dysplasia of the fibrous sheath in the flagellum principal piece., Results: The overall fertilization rate was 45%. The diploid embryo rate was 33%. Embryo quality was satisfactory. In five of six cycles, three embryos were transferred. Two triplet pregnancies were obtained corresponding to an implantation rate per transferred embryo of 40%., Conclusion: Total or extreme asthenozoospermia seems to be a good indication for SUZI.

This case report describes a patient presenting a cyst of the prostatic utricule that was detected during assessment for sterility and removed surgically. A review of the pertinent literature is proposed. Azoospermia or severe oligospermia associated with a low ejaculation volume are the main manifestations. Transrectal ultrasonography is the diagnostic examination of choice. In most cases incision of the mouth of the utricule promptly abolishes sterility and enables fertilization.

The value of partial zona dissection (PZD) was assessed in a randomized protocol of in-vitro fertilization (IVF) including 30 couples (44 cycles) with at least two sperm defects. Couples were divided into three groups according to previous IVF status, i.e. group I: total failure of previous IVF; group II: marginal success of previous IVF, and group III: no previous IVF. Both PZD and untreated oocytes were inseminated using the swim-across method. Although PZD did not enhance the overall proportion of fertilized eggs resulting in diploid cleaving embryos per retrieved oocyte (14.7 versus 17.1%), this rate was higher with PZD than with IVF when previous IVF attempts had failed (group I: 16.1 versus 4.5%, P < 0.01). The rate was similar for PZD and IVF in group II, and lower for PZD than IVF in group III (15.1 versus 30.8%, P < 0.01). The higher polyspermy rate associated with PZD in groups in which classical IVF worked, could partially explain these results. The role of a possible deleterious effect of PZD on the oocytes is discussed. Out of the 44 cycles, 20 reached the embryo transfer stage and four pregnancies were obtained. In our opinion PZD should be carried out in cases of sperm defects only when previous IVF attempts have failed.

Failure of in vitro fertilization or very low cleavage rates may occur even though oocyte and semen parameters seem satisfactory. Quantified ultrastructural study of spermatozoa was performed in such cases of failure (n = 6) or low cleavage rate (< 20%; n = 4). Through 1 to 11 retrievals, the number of inseminated oocytes ranged from 14 to 145. The results were compared to those of six fertile men. Quantification was achieved by cataloguing cell defects of the spermatozoon heads and mid-/principal pieces of the flagella. Using the data from each specimen, the percentages of total cellular abnormalities in the head/mid-/principal pieces were established. At the level of the head overall percentages for six groups of defects were determined. The overall percentage of combined head abnormalities, defined as the presence of at least three of these six defects on the same spermatozoon head, was established. Statistical differences among control and patient groups were analyzed by nonparametric Mann-Whitney U test. The percentages of anomalies of the midpiece and of the principal piece were not significantly different between patients and controls. Motility assessed by spermogram was considered "functionally uncompromised." In eight patients the percentage of cell alterations of the head (93-100 vs 77.3 +/- 6.4%) and the percentage of combined anomalies of the head (78.1-100 vs 60.8 +/- 8.5%) were significantly different between patients and controls. In two cases, the percentages established for all head parameters considered were not globally different from those observed in controls. Thus in 8 cases of 10, electron microscopy with quantified analysis supplied valuable evidence about the poor quality of these sperm samples judged as normal under light microscopy and may provide an explanation for their impaired fertilizability.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to evaluate a new method of in-vitro fertilization (IVF) in patients with severe sperm defects. Unlike the conventional swim-up method, spermatozoa and oocytes are placed in opposite corners of the bottom of the incubation dish so that sperm swimming is horizontal instead of vertical. Another difference between the swim-across and swim-up techniques is that the incubation medium is supplemented with 20% follicular fluid. After a randomized series (protocol I) of 15 IVF attempts had demonstrated that swim-across was more effective than swim-up in terms of fertilization and cleavage, we began a second series (protocol II) using only swim-across. A total of 124 couples with motile sperm counts less than 1 x 10(6) spermatozoa/ml of semen were included in protocol II. Clinical parameters (age, tubal damage) and number of recovered oocytes were recorded and compared in patients who did (group A: n = 94) and did not (group B: n = 74) achieve fertilization. In group A the fertilization rate was 36.7% and, out of the 94 transfers that were made, there were 21 clinical pregnancies and 12 full-term pregnancies with 16 live births. The number of oocytes collected (12 versus 7.7, P less than 0.001) and the incidence of tubal damage (50% versus 24.3%, P less than 0.001) was significantly higher in group A than in group B. Using logistic regression analysis, we showed a significant correlation between fertilization and progressive motility, percentage normal spermatozoa, number of recovered oocytes and tubal damage.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors report the results of an open multicentric study of 136 women treated by a combination of 35 micrograms ethinylestradiol and 2 mg cyproterone acetate for cutaneous manifestation of hyperandrogenism. No pregnancy occurred during the treatment of 12 months. Comparison between the last treated and non treated cycle showed a significant difference (p less than 0.001) in the severity of acne lesions regardless of their sites. General and gynaecological tolerance were excellent.

Every sperm parameter has an effect on the chances of fertilization. When fertilization has been obtained with a sperm, the cleavage rate is identical regardless of the count, the mobility or the results of the migration test. On the contrary, in case of teratospermia, the cleavage rate of fertilizing sperms is significantly decreased. The rate of pregnancy by transfer is identical with normal sperm and sperm deficiency.

In primary hypogonadism (n=73) FSH basal levels and responses are elevated. LH basal levels and/or responses are elevated in 68 cases. In idiophatic oligospermia FSH and/or response are elevated in 28% cases, normal in 68% cases, decreased in 4% cases. LH and/or LH response are elevated in 44% cases normal in 53% cases and decreased in 4% cases. High significant correlation is found between FSH basal levels and FSH response, and between FSH and LH response.

Basal concentrations of FSH, LH, testosterone, delta4 androstenedione and dihydrotestosterone, together with FSH and LH responses to single injections of LHRH were determined in eighty-four patients with oligospermia and in twenty-seven normal men. LHRH responses were heterogeneous and indicate that various disorders might cause this syndrome. In six cases there appeared to be an isolated deficiency in spermatogenesis, as indicated by an increased FSH response, whilst the LH response was normal as were the concentrations of the testicular hormones. In twenty cases a concomitant disorder of Leydig cell function and spermatogenesis is suggested as indicated by increased FSH and LH responses and decreased concentrations of testosterone and delta4 androstenedione (six) or concentrations at the lower limit of normal (fourteen). Furthermore, in five cases a hypothalamic and/or pituitary disturbance may be accepted on the basis of normal or decreased basal concentrations decreased and responses to LHRH with decreased concentrations of testosterone and delta4 androstenedione. Finally, in thirty-seven cases, oligospermia was not associated with any modification basal gonadotrophin concentrations or response to LHRH when compared with normal subjects.

Male hypogonadotropic hypogonadism is a rare disease but a caracteristic one of currently isolated gonadotropin deficiency. 15 subjects have been treated during 6 to 52 monthes with Neopergonal (225 UI a week) + H.C.G. (15 00 IU a week). We observed spermatogenesis onset in 11 patients, sufficient 9 of them, poor in 2 others.

Effects on plasma T, DHT, A, FSH, LH and PRL concentrations and the pituitary responsiveness to the LHRH/TRH stimulation, as well as on libido and sexual, mental and physical activities were studied in ten hypogonadal male patients undergoing therapy with oral testosterone undecanoate (TU) for 9 weeks. The daily dose of TU needed for satisfactory clinical effect was 120 mg (6 cases) and 240 mg (4 cases). There was a significant rise in circulation androgen concentrations in all patients. Mean plasma T, DHT and A increased at 9 weeks from 1.20, 0.12 and 0.36 ng/ml to 4.34 (P less than 0.0004), 0.39 (P less than 0.0004) and 1.24 ng/ml (P less than 0.005), respectively. In hypergonadotrophic patients (N = 6) plasma FSH and LH fell progressively (P less than 0.05), while in hypogonadotrophic patients (N = 4) a marked rise in plasma FSH (P less than 0.05) was found, while LH tended to rise as well. Base-line plasma PRL remained unchanged. In three out of four patients with poor PRL response to TRH, normal responses were established after TU therapy. Increase in libido and sexual activity was reported by nine patients. An increase in mental and physical activity was found in seven and two patients, respectively. Tolerance was excellent. It was concluded that oral TU is an effective form of substitution therapy in male hypogonadal patients.

The aim of this study was to examine if it was possible to simplify the procedure of some stimulation tests of pituitary function. This study was performed on 300 stimulation tests of TSH by TRH, PRL by TRH, LH by LHRH and FSH by LHRH, respectively. Simplified procedures may be proposed without altering the diagnostic value of the tests: assay of TSH and PRL 0 and 30 minutes after TRH injection and of LH and FSH 0, 30 and 60 minutes after LHRH injection.

Among 1,000 couples requesting for AID at CECOS Sud-Est in Marseille azoospermia is found in 572, oligoasthenozoospermia in 395. Cryptorchidism is recorded in 20% of these men. Several hypofertility factors are frequently associated. Ejaculation is absent in 23 men. 10 couples are requesting for AID because a risk of severe autosomic disease. Mean success rate is 10% per cycle, increased by sperm quality, decreased in women older than 35 years.

The series of events, evidenced in animals after a single injection of human chorionic gonadotrophin (hCG): down-regulation of LH/hCG membrane receptors, uncoupling between receptors and the adenylate cyclase, also includes a blockade of testicular steroidogenesis beyond cyclic-AMP formation, including an inhibition of the 17 alpha-hydroxylase-17, 20-desmolase enzymatic complex. This complex phenomenon, named hCG-induced testicular desensitization also occurs in adult men. Since it is not known if and when these effects are initiated during sexual maturation, we have investigated the kinetics of responses of plasma testosterone (T), its two immediate precursors, delta 4-androstenedione (delta 4) and 17 alpha-hydroxprogesterone (OHP), and 17 beta-estradiol (E2) for a week after a single injection of hCG given at the same dosage (100 IU/kg body weight) in subjects not yet exposed to adult levels of endogenous LH, ie prepubertal boys and untreated hypogonadotrophic hypogonadic (HH) adult men. The HH subjects have been restudied after 3 months of a weekly injection of the hCG at the same dosage. In immature individuals, the effect of hCG on testicular steroidogenisis was strikingly different from that observed previously in adults: in the former, whether prepubertal boys or untreated HH adults, a single hCG injection induced a progressive and substantial rise in plasma T, maximal at 96-120 h, a modest and late rise in E2, but no significant change in delta 4 or OHP. In contrast, in adult men there is a dissociation between the responses of plasma T and delta 4 (maximal at about 72 h) to hCG and those of OHP and E2 which peak at about 24 h. After 3 months of hCG-treatment the adult pattern was induced in HH patients: early and significant rise in OHP and E2. This suggests that a pre-exposure to LH/hCG is necessary for hCG-induced testicular desensitization, at least for its enzymatic expression. A stimulatory effect of hCG on a testicular aromatase and an inhibitory effect on the 17, 20-desmolase are observed concomitantly in relation to age or to previous gonadotropin environment. It still remains uncertain to conclude that the former effect is directly responsible for the latter.

Twenty-six patients with Graves' hyperthyroidism treated only with propranolol for 1-21 months have been followed up to 5 years. The patients were evaluated before treatment, at 15, 30, and 90 days during treatment, and then at 90-day intervals during propranolol treatment by clinical examination and measurement of serum free T3, free T4, rT3, TSH, and sex hormone-binding globulin concentrations and serum anti-thyroglobulin, antithyroid microsomal, antithyroid peroxidase, and thyroid-stimulating autoantibodies. Eighteen patients who had no biochemical improvement during propranolol therapy or relapsed after initial improvement were treated conventionally. In contrast, eight patients had a biochemical remission, which has lasted 30-48 months after propranolol withdrawal. The biochemical values before and during treatment did not differ among the two groups of patients, except for the initial serum free T3 levels which were significantly higher in the patients who had no remission. Serum TSH levels returned to normal only in patients who had a long-lasting remission. While thyroid autoantibodies decreased or disappeared during follow-up, the evolution of thyroid-stimulating autoantibody values was grossly related to the clinical outcome. Long-lasting remissions may occur in patients with hyperthyroidism due to Graves' disease not given ablative or antithyroid drug therapy. Since propranolol is devoid of antithyroid and immunosuppressive actions, these remissions are probably spontaneous. Although they tended to occur in patients with less severe disease, no biological parameter was found that predicted the outcome.

Alterations in the secretion of iodothyronines, cortisol, testosterone and growth hormone have previously been described in anorexia nervosa. We have studied prolactin and gonadotropins secretion in 23 cases of anorexia nervosa. Prolactin secretion was normal. Modifications in gonadotropins release were observed. However they could not be always related to weight loss since amenorrhea could either precede weight loss or still be present after return of the weight to normal. In all cases, FSH release after LHRH stimulation was normal. No increase in LH levels was observed after LHRH injection when the weight was 70% below the ideal weight. With increasing weight, LH release progressively recovered and normal LHRH-induced LH release was obtained when the weight was above 90% of the ideal weight. At normal weight, the ratio of LH/FSH was normal in patients menstruating less than 3 months after the test, while the ratio was low in non-menstruating females. In conclusion, when the weight was insufficient basal levels of FSH and LH and responses after LHRH stimulation corresponded to a prepuberal stage. An increase in the LH/FSH ratio and a normal LH/FSH ratio preceeded the recovery of menstruations. In about 1/3 of the cases, such an evolution was not observed without any satisfactory explanation. Other factors than weight may be involved, especially when the amenorrhea persists after weight recovery.

To examine the mechanism of bromocriptine effects in patients suffering from benign prostatic hypertrophy (BPH), urinary prostaglandin E2 (PGE2) contents were investigated before and during treatment. An active PGE2 synthesis was detected within the BPH area. Yet, PGE2 concentration in urine could be related neither to the severity of disease nor to the clinical response observed in patients under bromocriptine therapy. Under treatment, a considerable urodynamic improvement was observed in 75% of patients suffering from BPH. In these cases, the prostatic hypertrophy was not markedly reduced. PGE2 urinary contents lowered under treatment provided a beneficial clinical response in patients. The results are discussed with respect to PGE2 involvement in the mechanism of action of prolactin. It is suggested that a direct role of PGE2 and a local effect of bromocriptine in BPH urinary dysfunctioning of the lower urinary tract could not be excluded.

The TSH-displacing and the thyroid-stimulating activities of Graves' immunoglobulins G (GIgG) have been accounted for by either homogeneous TSH receptor antibodies or heterogeneous antibodies directed toward the TSH receptor-adenylate cyclase system. To clarify this matter, the study of the interactions of GIgG preparations from 14 untreated Graves' patients with human thyroid membranes was undertaken. Dose-response curves of GIgG, diluted in IgG from normal subjects, were carried out in the [125I]TSH radioreceptor assay and the adenylate cyclase assay in the presence or absence of TSH. In the radioreceptor assay, GIgG were constantly negative in 3 cases (21%) and positive, depending of the dose, in 11 cases. In the adenylate cyclase assay, the dose-activity profiles in the absence of TSH were bell-shaped curves in 3 cases and sigmoid curves in 9 cases; in 2 cases (14%), GIgG preparations were devoid of any effect. Binding-isotherms and dose-activity profiles did not appear to share simple relationships. In the presence of TSH, GIgG preparations elicited a decrease in 6 cases, an increase in 3 cases, and no effect in 5 cases (36%) in the adenylate cyclase activity. The data obtained by radioreceptor assay and adenylate cyclase assay in the presence or absence of TSH were found statistically correlated (P less than 0.05 to P less than 0.001) but not linearly related, the points being scattered on specific parts of the diagrams. These observations could not be accounted for by TSH receptor antibodies in GIgG being an entity of constant properties, albeit varying in titer among patients. Rather, GIgG effects fit well the patterns of action of a heterogeneous ligand, as shown by computing a theoretical model for ligand heterogeneity with respect to binding equilibrium constant and intrinsic biological activity. Accordingly, GIgG activity in the TSH receptor-adenylate cyclase system could be attributed to heterogeneous antibodies varying with regard to binding constant and acting as stimulating or blocking antibodies of the adenylate cyclase.

Plasma levels of FSH and LH, in 232 subjects examined for sterility or hypogonadism, have been assessed vefore and after stimulation by LH RH (100 microng IV). In excretory azoospermia, the basal levels as well as the response to LH RH of FSH as well as LH are normal. In early testicular damage (constitutional or acquired); basal FSH levels are elevated (91% of the cases) as well as the FSH response to LH RH (78%); basal LH levels are either normal (66% of the cases) or elevated (34%). An augmentation of the LH response has been found in 92% of the cases. In hypogonadotrophic hypogonadism (n = 12) 3 types of responses have been noticed : absence of response of FSH and of LH (7 cases); normal FSH response, no LH response (2 cases); exaggerated FSH and LH response (2 cases). In idiopahtic oligospermia (n = 84); basal FSH levels are elevated in 24 cases but normal in the rest. There is a highly significant correlation between basal FSH and its response to LH RH injection (r = 0.73, t = 9,67 p less than 0,001); basal LH levels are normal, except in 5 cases where a definite increase has been noted. The response of LH is exaggerated in 36 cases which includes the 5 showing enhanced basal LH levels. There is a highly significant correlation between FSH response and LH response (r = 0,55; t = 5,94; p less than 0,001). Exploration of patients with varicocoele intact or operated show no difference from those suffering from idiopathic oligospermia. From a practical point of view, the LH RH test enables : a distinction between excretory azoospermia and secretory azoospermia with normal testicular volume, without recourse to testicular biopsy; affirmation, in 36% of cases with idiopathic oligospermia of the early damage to spermatogenesis, thus contra-indicating any treatment involving testicular stimulation. From the physico-pathological point of view : the early damage to spermatogenesis is characterized by an elevation in basal FSH and its response to LH RH injection. The significance of the augmented Lh response, which often accompanies an augmentation in FSH response but incertain cases is isolated, is discussed.