Index

Serono acquires exclusive rights to cetrotide®

Serono S.A. announced that it has acquired exclusive rights from ASTA Medica to market, distribute and sell Cetrotide® (cetrorelix acetate for injection) in the US and worldwide, with the exception of Japan, for the indication of controlled ovarian stimulation prior to Assisted Reproductive Technologies (ART). Last month, Cetrotide® received marketing approval from the US Food and Drug Administration (FDA) under a new drug application (NDA) filed by ASTA Medica. As a consequence of the new agreement between Serono and ASTA Medica, the Cetrotide® NDA will be transferred to Serono. Cetrotide®, a gonadotropin releasing hormone (GnRH) antagonist, offers a new and convenient treatment to prevent premature ovulation in women undergoing controlled ovarian stimulation for ART. Cetrotide® was developed by ASTA Medica and became the first GnRH antagonist to be available anywhere in the world when it received European marketing authorization for this indication in April 1999. Cetrotide® has been successfully introduced by Serono and ASTA Medica in more than 10 European countries. The FDA approval of Cetrotide® will boost its position as the top-selling GnRH antagonist in the world. Serono expects to launch Cetrotide® in the US by the first quarter of 2001.
For more information, please go to www.serono.com

Smoking is associated with the retention of cytoplasm by human spermatozoa

Mak V, Jarvi K, Buckspan M, Freeman M, Hechter S, Zini A
Division of Urology, Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

Objectives. To determine whether cigarette smoking is associated with the abnormal retention of residual sperm cytoplasm in infertile men.Methods. Semen samples were obtained from 87 consecutive non-azoospermic men with idiopathic infertility (18 smokers and 69 nonsmokers) and from 20 men presenting for vasectomy (fertile controls). Standard semen parameters and the percentage of spermatozoa with residual cytoplasm (on Papanicolaou smears) were recorded.Results. Subject age, semen volume, and sperm density, motility, and morphology were not significantly different between the two groups of infertile men. However, a significant difference was found in the mean +/- SEM percentages of sperm with cytoplasm droplets between smokers and nonsmokers (12.9% +/- 1.7% and 8.1% +/- 0.9%, respectively; P < 0.001).Conclusions. Our data suggest that cigarette smoking is associated with retention of sperm cytoplasmic droplets in infertile men, a morphologic characteristic associated with impaired sperm function.
Urology 2000 Sep 1;56(3):463-6

Source: www.ncbi.nlm.nih.gov

Screening for AZF deletion in a large series of severely impaired spermatogenesis patients

Martinez MC, Bernabe MJ, Gomez E, Ballesteros A, Landeras J, Glover G, Gil-Salom M, Remohi J, Pellicer A
Equipo-IVI-Murcia, Spain

Recent investigations have pointed to a high prevalence of Y chromosome submicroscopic deletions in men with severely impaired spermatogenesis. We report on the incidence in 128 infertile men, in whom karyotype, sperm count, and hormonal parameters were evaluated. Patients with abnormal karyotype (other than an abnormal Y chromosome) or sperm concentration of more than 2 million/mL were excluded. Genomic DNA was extracted from the peripheral leukocytes of 57 men with azoospermia and 71 with severe oligospermia. Molecular analysis was performed by 3 multiplex polymerase chain reactions using a set of 9 sequence tagged sites (STSs) from 3 different regions of the Y chromosome: AZFa, AZFb, and AZFc. In 7% of the studied patients Yq microdeletions were detected, with a high prevalence in men with azoospermia (14%). No deletions were detected in the AZFa region. Deletions were present in AZFb, AZFc, or both regions. The deletion observed in 1 patient that did not overlap with the DAZ region demonstrates that genes other than DAZ may also be involved in the pathogenesis of some subsets of male infertility. Furthermore, common Yq deletions present different testicular pictures, suggesting that some unknown factors may be disturbing spermatogenesis. Because men with severe infertility suffer a high risk of Y chromosome deletion, screening for these men is recommended prior to treatment with assisted reproduction.
J Androl 2000 Sep-Oct;21(5):651-5

Source: www.ncbi.nlm.nih.gov

A randomized study of the effect of 10 minutes of bed rest after intrauterine insemination

Saleh A, Tan SL, Biljan MM, Tulandi T
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada

Objective: To evaluate the effects of 10 minutes of bed rest after intrauterine insemination (IUI) on the pregnancy rate.Design: Prospective randomized study.Setting: University teaching hospital.Patient(s): One hundred sixteen couples with unexplained infertility.Intervention(s): Patients were prospectively randomized either to immediate mobilization after IUI (group I) or to remain in a supine position for 10 minutes after the procedure (group II).Main Outcome Measure(s): Cumulative pregnancy rate.Result(s): Ninety-five couples were included in the analysis. Group I consisted of 40 couples (90 cycles), and group II consisted of 55 couples (120 cycles). The pregnancy rate per couple in group I (4 of 40 [10%]) was significantly lower than in group II (16 of 55 [29%]). The pregnancy rate per cycle in group I (4.4%) was also lower than in group II (13.3%). With use of life-table analysis, the cumulative probability of pregnancy in group II was significantly higher than in group I.Conclusion(s): A 10-minute interval of bed rest after IUI has a positive effect on the pregnancy rate. We recommend that mandatory bed rest for 10 minutes after IUI should be adopted into a standard practice.
Fertil Steril 2000 Sep 1;74(3):509-511

Source: www.ncbi.nlm.nih.gov

Bleeding and spontaneous abortion after therapy for infertility

Pezeshki K, Feldman J, Stein DE, Lobel SM, Grazi RV
Division of Reproductive Endocrinology and Infertility, Maimonides Medical Center, Brooklyn, New York, USA

Objective: To determine the incidence of early-pregnancy bleeding and spontaneous abortion (SAB) after various treatments for infertility and to assess whether bleeding is predictive of SAB.Design: An historic cohort study of women who conceived after various treatments.Setting: Hospital-based private practice.Patient(s): We studied 418 patients in whom 500 consecutive clinical pregnancies occurred.Intervention(s): Patients were grouped according to the method of conception: ovulation induction, IVF, and other. The latter category included interventions not requiring ovulation induction, such as surgery and insemination. A fourth group of subjects who conceived independently of treatment was used as the control.Main Outcome Measure(s): Bleeding and pregnancy outcome (SAB, ectopic pregnancy, or ongoing pregnancy).Result(s): Rates of SAB did not differ among the treatment groups. SAB occurred significantly more often after bleeding than when bleeding did not occur (30.8% versus 19.8%, respectively). Bleeding was predictive of SAB only in patients <35 years old (odds ratio 2.4).Conclusion(s): Infertile women who conceive after reproductive therapy are not at increased risk for SAB compared with women who conceive naturally. There appears to be no association between previous diagnosis or treatment and the occurrence of SAB in previously infertile women. Bleeding is associated with a twofold relative risk of SAB.
Fertil Steril 2000 Sep 1;74(3):504-508

Source: www.ncbi.nlm.nih.gov

Relationship between classic histological pattern and sperm findings on fine needle aspiration map in infertile men

Meng MV, Cha I, Ljung BM, Turek PJ
Departments of Urology and Pathology, University of California San Francisco School of Medicine, San Francisco, California, USA

Systematic testis fine needle aspiration (FNA) mapping has been proposed as an adjunctive or alternative diagnostic procedure to biopsy to determine the presence of spermatozoa within infertile testes. This study related testis histology to the global presence or absence of spermatozoa in the same testes determined by FNA cytology. Testis biopsies and FNA mapping were performed in 87 infertile, azoospermic men. A mean of 1.3 biopsies and 14 FNA sites were taken per patient. Biopsies were assessed by recognized histological patterns of normal, Sertoli cell-only, hypospermatogenesis, early and late maturation arrest, sclerosis as well as mixed patterns that included at least two of these histologies. FNA cytological specimens were assessed for sperm presence by an experienced cytologist. Overall, spermatozoa were found by FNA mapping in 52% of patients. A comparison of histology and FNA findings revealed that pure patterns of Sertoli cell-only and early maturation were associated with a very poor likelihood of sperm detection (4-8%). In contrast, patients with other pure pattern histologies or mixed patterns had high rates of FNA sperm detection (77-100%). Similar to reported testicular sperm extraction (TESE) findings, sperm detection with FNA shows wide variation depending on testis histology. Unlike most TESE reports, however, some histological patterns generally reflect a more global testicular dysfunction and poorer likelihood of sperm identification, suggesting the possibility that these phenotypes have a genetic origin. Systematic testis sampling with FNA offers additional geographical information about spermatogenesis that routine biopsies lack and can further guide couple decision-making in severe male factor infertility.
Hum Reprod 2000 Sep;15(9):1973-1977

Source: humrep.oupjournals.org

Stress-response in male partners of women submitted to in vitro fertilization and embryo transfer

Tarabusi M, Matteo ML, Volpe A, Facchinetti F
Department of Obstetrics, Gynecology and Pediatric Sciences, University of Modena, Italy

Background: In a previous work, we have reported the relationship between women and the outcome of in vitro fertilization and embryo transfer (IVF-ET). The goal of the present work is to evaluate the association between vulnerability to stress and treatment outcome in male partners of couples submitted to IVF-ET. Methods: The day of semen collection at the Assisted Reproduction Unit of the Department of Obstetrics and Gynecology, University of Modena, 45 subjects were submitted to Stroop Color Word Conflict, a task measuring the ability to cope with a cognitive stressor, involving the attentional and sympathoadrenal system. Systolic and diastolic blood pressure, as well as heart rate (HR), were measured at baseline, during the test and 10 min after the end of testing. The evidence of pregnancy (betahCG >250 mIU/ml 12 days after ET) is the main outcome measure; the couples were classed in either a 'success' or a 'failure' group. Results: Thirteen couples became pregnant. Pregnancy progressed until term in 6 cases, while 7 cases showed only a preclinical evidence of pregnancy. Age, education, causes and duration of infertility were similar in the success and failure groups. No difference was found in the number and motility of spermatozoa both at baseline and after capacitation (a technique improving sperm motility). Moreover, the success group showed a higher number of both fertilized oocytes and embryos transferred compared with the failure group. The area under the curve of the cardiovascular parameters was calculated. The failure group showed a higher value for HR (50.6 +/- 36.7 of percent total change) than the success group (31.8 +/- 16.9; p = 0.006). Conclusions: The cardiovascular response to stress is a good correlate of success in infertile males submitted to the IVF-ET program.
Psychother Psychosom 2000 Sep-Oct;69(5):275-9

Source: www.online.karger.com

CAG trinucleotide repeats in the androgen receptor gene of infertile men exhibit stable inheritance in female offspring conceived after ICSI

Cram DS, Song B, McLachlan RI, Trounson AO
Monash IVF, Australia, Monash Institute of Reproduction and Development, Clayton 3168, Australia, and. Prince Henry's Institute of Medical Research

The androgen receptor (AR) gene is located on the X chromosome and contains a polymorphic CAG tract. CAG repeat expansions in the AR have been associated with male infertility and the neuromuscular disease, spinal bulbar muscular atrophy (SBMA). Based on Mendelian inheritance patterns, moderate CAG expansions in infertile men treated by intracytoplasmic sperm injection (ICSI) would be vertically transmitted to female offspring. Should further elongation of the repeat region occur in the male germline, it is conceivable that longer expansions could also be transmitted by ICSI and may lead to an increased incidence of male infertility and SBMA in succeeding generations. To determine the degree of stability of the paternal AR CAG tract following ICSI, we compared the CAG repeat number in the AR alleles of 92 men presenting for ICSI and their 99 ICSI-conceived daughters. CAG repeat lengths in the AR alleles were determined by fluorescent polymerase chain reaction and Genescan analysis of amplification products separated on DNA sequencing gels. In the vast majority of cases (95 out of 99), we found that the AR CAG tracts ranging in size from 15-28 repeats exhibited stable inheritance in female offspring. However, in the remaining father-daughter pairs, there was a discordance in the expected inheritance pattern with evidence for both CAG expansion (20-->24; 22-->23) and contraction (26-->18 or 22) of the paternal AR allele. The detection of a low frequency of CAG mutation in paternal AR alleles following ICSI would be consistent with gonadal mosaicism originating from meiotic DNA replication errors. These findings in a typical group of infertile men undergoing ICSI for a variety of indications tend to alleviate concerns that ICSI may promote the transmission of AR alleles with expanded CAG tracts and suggest that the risk of SBMA in second generation sons would be extremely low.
Mol Hum Reprod 2000 Sep;6(9):861-6

Source: molehr.oupjournals.org

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