FERTI.NET HIGHLIGHTS
Issue 17 - Week 34 - Volume 2 - 2000
Ferti.Net Highlights Archive

This fortnightly news service brings you the latest news on Assisted Reproduction Techniques as they have been reported in the media. Sources include on-line media, medical data bases, original press releases, trade journals, national daily newspapers and broadcasts reports, as well as peer-reviewed publications. It also keeps you up-to-date with the latest issue of the Ferti.Net Magazine.

Y chromosome microdeletions and germinal mosaicism in infertile males

Le Bourhis C, Siffroi JP, McElreavey K, Dadoune JP
Service d'Histologie, Biologie de la Reproduction et Cytogenetique et CECOS, Hopital Tenon, Paris, and Laboratoire d'Immunogenetique Humaine, Institut Pasteur, Paris, France

Molecular deletions of the Y chromosome long arm are a frequent cause of male infertility. Because these deletions are thought to be inherited from fathers without Y chromosome deletions, the question arises as to whether their relatively high incidence in the male population could be due to the existence of a mosaicism in somatic and/or germinal paternal cells. This study included a total of 181 infertile men, among whom 18 were found to have an abnormal karyotype. In the other 163, polymerase chain reaction (PCR) analysis detected nine (5.5%) Y chromosome microdeletions. Blood, spermatozoa or testicular cells from 47 men (27 oligozoospermia, 20 azoospermia), including six Y-deleted patients, were screened for mosaicism using double target fluorescence in-situ hybridization (FISH) with Y centromeric and deleted in azoospermia (DAZ) gene-specific probes. Results indicated that: (i) percentages of double (intact Y chromosome) or single (deleted Y chromosome) fluorescent signals by FISH were in agreement with PCR data, thus demonstrating the reliability of the method; and (ii) a weak germ cell mosaicism was found in only two oligozoospermic patients, carrying 1.97 and 4.13% respectively of spermatozoa with a deleted Y chromosome. Further studies on larger populations are needed to evaluate precisely the incidence of Y deletion mosaicisms in infertile men.
Mol Hum Reprod 2000 Aug;6(8):688-693

Source: molehr.oupjournals.org

Gonadotropin-Releasing Hormone-Stimulated Sperm Binding to the Human Zona Is Mediated by a Calcium Influx

Morales P, Pizarro E, Kong M, Kerr B, Ceric F, Vigil P
Unit of Reproductive Biology, Faculty of Health Sciences, University of Antofagasta, Antofagasta, Chile. Faculty of Biological Sciences, P. Catholic University of Chile, Santiago, Chile

The mechanism by which GnRH increases sperm-zona pellucida binding in humans was investigated in this study. We tested whether GnRH increases sperm-zona binding in Ca(2+)-free medium and in the presence of Ca(2+) channel antagonists. We also examined the GnRH effect on the intracellular free Ca(2+) concentration ([Ca(2+)](i)). Sperm treatment with GnRH increased sperm-zona binding 300% but only when Ca(2+) was present in the medium. In Ca(2+)-free medium or in the presence of 400 nM nifedipine, 80 muM diltiazem, or 50 muM verapamil, GnRH did not influence sperm-zona binding. GnRH increased the [Ca(2+)](i) in the sperm in a dose-dependent manner. The maximum effect was reached with 75 nM GnRH. The GnRH-induced increase in [Ca(2+)](i) was fast and transient, from a basal [Ca(2+)](i) of 413 +/- 22 nM to a peak value of 797 +/- 24 nM. The GnRH-induced increase in [Ca(2+)](i) was entirely due to a Ca(2+) influx from the extracellular medium because the increase in [Ca(2+)](i) was blocked by the Ca(2+) chelator EGTA and by the Ca(2+) channel antagonists nifedipine and diltiazem. These antagonists, however, were not able to inhibit the progesterone-activated Ca(2+) influx. On the contrary, T-type calcium channel antagonists pimozide and mibefradil did not affect GnRH-activated Ca(2+) influx but inhibited the progesterone-activated Ca(2+) influx. Finally, the GnRH-induced Ca(2+) influx was blocked by two specific GnRH antagonists, Ac-D-Nal(1)-Cl-D-Phe(2)-3-Pyr-D-Ala(3)-Arg(5)-D-Glu(AA)(6)-GnRH and Ac-(3,4)-dehydro-Pro(1),-p-fluoro-D-Phe(2), D-Trp(3,6)-GnRH. These results suggest that GnRH increases sperm-zona binding via an elevation of [Ca(2+)](i) through T-type, voltage-operated calcium channels.
Biol Reprod 2000 Aug;63(2):635-642

Source: www.biolreprod.org

Development of brief stress management support groups for couples undergoing in vitro fertilization treatment

McNaughton-Cassill ME, Bostwick M, Vanscoy SE, Arthur NJ, Hickman TN, Robinson RD, Neal GS
Division of Behavioral and Cultural Sciences, University of Texas at San Antonio, USA

OBJECTIVE: To develop and assess the efficacy of couples stress management groups offered concurrently with IVF treatment. DESIGN: Couples in IVF treatment were given the option of participating in a biweekly stress management group. SETTING: The IVF treatment clinic at Wilford Hall Medical Center, San Antonio, Texas. PATIENT(S): One or both members of 17 couples participated in the program in one of four group cycles. INTERVENTION(S): A cognitive behavioral treatment model was used to help couples process their feelings and cognitions about the impact of infertility on their life and explore their expectations about their future options for becoming parents. MAIN OUTCOME MEASURE(S): Couples were asked to anonymously evaluate the efficacy of the group after they had completed their IVF cycle. RESULT(S): Participants reported that the group helped them deal with the stress of infertility and that they valued the social bonds they formed with other group members. CONCLUSION(S): These data suggest that brief focused group therapy, offered while couples are undergoing IVF, is an effective way to help people deal with the stress of infertility treatment.
Fertil Steril 2000 Jul;74(1):87-93

Source: www.ncbi.nlm.nih.gov

Multiple gestation pregnancy

The ESHRE Capri Workshop Group*

Multiple gestation pregnancy rates are high in assisted reproductive treatment cycles because of the perceived need to stimulate excess follicles and transfer excess embryos in order to achieve reasonable pregnancy rates. Perinatal mortality rates are, however, 4-fold higher for twins and 6-fold higher for triplets than for singletons. Since the goal of infertility therapy is a healthy child, and multiple gestation puts that goal at risk, multiple pregnancy must be regarded as a serious complication of assisted reproductive treatment cycles. The 1999 ESHRE Capri Workshop addressed the psychological, medical, social and financial implications of multiple pregnancy and discussed how it might be prevented. Multiple gestations are high risk pregnancies which may be complicated by prematurity, low birthweight, pre-eclampsia, anaemia, postpartum haemorrhage, intrauterine growth restriction, neonatal morbidity and high neonatal and infant mortality. Multiple gestation children may suffer long-term consequences of perinatal complications, including cerebral palsy and learning disabilities. Prevention is the most important means of decreasing multiple gestation rates. Multiple gestation rates in ovulation induction and superovulation cycles can be reduced by using lower dosage gonadotrophin regimens. If there are more than three mature follicles, the cycle should be converted to an IVF cycle, or it should be cancelled and intercourse should be avoided. In IVF cycles two embryos can be transferred without reducing birth rates in most circumstances. Embryo reduction involves extremely difficult decisions for infertile couples and should be used only as a last resort. Reducing the multiple gestation pregnancy rate should be a high priority for assisted reproductive treatment programmes, despite the pressure from some patients to transfer more embryos in order to improve success.
Hum Reprod 2000 Aug;15(8):1856-1864

Source: humrep.oupjournals.org

Polycystic ovary syndrome, infertility, familial thrombophilia, familial hypofibrinolysis, recurrent loss of in vitro fertilized embryos, and miscarriage

Glueck CJ, Awadalla SG, Phillips H, Cameron D, Wang P, Fontaine RN
Cholesterol Center, Jewish Hospital, Cincinnati, Ohio, USA

Objective: To study reversible determinants of infertility and recurrent loss of transferred embryos after failure of 7 of 10 embryo transfers, 1 live birth, and 2 miscarriages. Design: Measures of thrombophilia, hypofibrinolysis, reproductive hormones, and androgenic steroids before and after metformin therapy.Setting: Outpatient clinical research center. Patient(s): A 32-year-old amenorrheic, infertile woman with polycystic ovary syndrome (PCOS) who had 7 of 10 embryo transfers fail, 1 premature live birth, and 2 miscarriages at 8 and 17 weeks.Intervention(s): Metformin (2.55 g/d) was given to ameliorate the endocrinopathy of PCOS. Main Outcome Measure(s): Coagulation, insulin, reproductive hormones, and androgenic steroids. Result(s): The propositus had thrombophilia (familial protein S deficiency [free protein S 32%; normal >/=65%]). She also had familial hypofibrinolysis with 4G4G polymorphism of the plasminogen activator inhibitor (PAI-1) gene and high PAI-1 activity (PAI-Fx), 42.5 U/mL, normal <21.1. Polycystic ovary syndrome was characterized by amenorrhea, polycystic ovaries, high fasting serum insulin (39 muU/mL, normal <20), androstenedione (763 ng/dL, normal <250), and testosterone (229 ng/dL, normal <83). After she received metformin for 4 months, PAI-Fx normalized (12.4 U/mL), as did insulin (12 muU/mL), androstenedione (185 ng/dL), and testosterone (39 ng/dL); weight fell from 109 to 91.3 kg (16%). Conclusion(s): Metformin reversed the endocrinopathy of PCOS. Familial thrombophilia and hypofibrinolysis may lead to thrombosis-mediated uteroplacental vascular insufficiency, failure to achieve pregnancy after embryo transfer, and miscarriage.
Fertil Steril 2000 Aug 1;74(2):394-397

Source: www.ncbi.nlm.nih.gov

Does assisted hatching pose a risk for monozygotic twinning in pregnancies conceived through in vitro fertilization?

Schieve LA, Meikle SF, Peterson HB, Jeng G, Burnett NM, Wilcox LS
Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Objective: To examine the association between assisted hatching and monozygotic (MZ) twinning.Design: Case-control.Setting: Population-based sample of IVF-ET cycles initiated in U.S. clinics, 1996.Patient(s): The IVF-ET (n = 35,503) cycles and 11,247 resultant pregnancies.Intervention(s): Use of an assisted hatching procedure on embryos transferred.Main Outcome Measure(s): Cases were pregnancies for which number of fetal hearts observed on ultrasound exceeded number of embryos transferred. These pregnancies were considered to contain at least one MZ set of twins. Cases were compared with two control groups: other multiple-gestation pregnancies (>/=2 fetal hearts but number of fetal hearts </= number of embryos transferred); and singleton pregnancies (1 fetal heart).Result(s): Women with a case pregnancy were more likely to have received embryos treated with assisted hatching procedures than were women in either control group. After adjustment for patient age, number of embryos transferred, prior cycles, infertility diagnosis, intracytoplasmic sperm injection, and whether embryos from the current cycle were cryopreserved for later use, odds ratios and 95% CIs for use of assisted hatching were 3.2 (1.2-8.0), compared with other multiple-gestation pregnancies, and 3.8 (1.8-9.8), compared with singleton pregnancies.Conclusion(s): Assisted hatching may pose a risk for MZ twinning.
Fertil Steril 2000 Aug 1;74(2):288-294

Source: www.ncbi.nlm.nih.gov

Ovarian stimulation during assisted reproduction treatment: a comparison of recombinant and highly purified urinary human FSH

Schats R, Sutter PD, Bassil S, Kremer JA, Tournaye H, Donnez J
Academic Hospital 'Vrije Universiteit' Amsterdam, Department of Obstetrics and Gynaecology, Amsterdam, the Netherlands, Centre for Infertility, University Hospital, Gent, Belgium, Catholic University of Louvain, Faculty of Medicine, Department of Gynaecology, St Luc's University Hospital, Brussels, Belgium, Academic Hospital St Radboud, Department of Obstetrics and Gynaecology, Nijmegen, the Netherlands, and Centre for Reproductive Medicine, University Hospital of the Dutch speaking Brussels Free University, Brussels, Belgium

This randomized, single-blind, multicentre, multinational study compared recombinant human FSH (rhFSH, Gonal-F((R))) with highly purified urinary human FSH (uhFSH, Metrodin HP((R))) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). Following desensitization in a long gonadotrophin-releasing hormone (GnRH) agonist protocol, patients received s.c. Gonal-F((R)) or Metrodin HP((R)), at a fixed dose of 150 IU, until there was adequate follicular development. Of 496 women randomized, 232 and 231 in the Gonal-F((R)) and Metrodin HP((R)) groups respectively received human chorionic gonadotrophin (HCG). The duration of FSH treatment was significantly shorter with Gonal-F((R)) than with Metrodin HP((R)) (11.6 +/- 1.9 days versus 12.4 +/- 2.7 days; P <0.0001) and significantly fewer ampoules were required (mean 22.6 +/- 5.0 versus 24.3 +/- 5.1, P <0.0002). There were, however, significantly more follicles >/=10 mm in diameter with Gonal-F((R)) (15.6 +/- 8.2 versus 13.6 +/- 7.1, P < 0.01) and oocytes retrieved (13.1 +/- 7.7 versus 11.4 +/- 7.6, P <0.002). Although no statistical difference in pregnancy rate was recorded, patients receiving Gonal-F((R)) had a higher pregnancy rate per cycle than patients given Metrodin HP((R)) (25.1 versus 20.1%). Moderate to severe ovarian hyperstimulation syndrome occurred in 2.8 and 1.2% of Gonal-F((R)) and Metrodin HP((R)) patients respectively (not significant). In conclusion, FSH stimulation in combination with a long GnRH agonist protocol is effective in inducing multiple follicular development and embryos with a high implantation potential. However, Gonal-F((R)) is clearly more effective than Metrodin HP((R)) in inducing multifollicular development.
Hum Reprod 2000 Aug;15(8):1691-1697

Source: humrep.oupjournals.org

Spermiogenesis and exchange of basic nuclear proteins are impaired in male germ cells lacking camk4

Wu JY, Ribar TJ, Cummings DE, Burton KA, McKnight GS, Means AR
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA

Ca2+/calmodulin-dependent protein kinase IV (Camk4; also known as CaMKIV), a multifunctional serine/threonine protein kinase with limited tissue distribution, has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells. In the mouse testis, however, Camk4 is expressed in spermatids and associated with chromatin and nuclear matrix. Elongating spermatids are not transcriptionally active, raising the possibility that Camk4 has a novel function in male germ cells. To investigate the role of Camk4 in spermatogenesis, we have generated mice with a targeted deletion of the gene Camk4. Male Camk4-/- mice are infertile with impairment of spermiogenesis in late elongating spermatids. The sequential deposition of sperm basic nuclear proteins on chromatin is disrupted, with a specific loss of protamine-2 and prolonged retention of transition protein-2 (Tnp2) in step-15 spermatids. Protamine-2 is phosphorylated by Camk4 in vitro, implicating a connection between Camk4 signalling and the exchange of basic nuclear proteins in mammalian male germ cells. Defects in protamine-2 have been identified in sperm of infertile men, suggesting that our results may have clinical implications for the understanding of human male infertility.
Nat Genet 2000 Aug;25(4):448-52

Source: www.nature.com

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