Bernd Hinney

Segregation of sex chromosomes into sperm nuclei in a man with 47,XXY Klinefelter's karyotype: a FISH analysis.

Abstract Meiotic segregation of the sex chromosomes was analysed in sperm nuclei from a man with Klinefelter’s karyotype by three-colour FISH. The X- and Y-specific DNA probes were co-hybridized with a probe specific for chromosome 1, thus allowing diploid and hyperhaploid spermatozoa to be distinguished. A total of 2206 sperm nuclei was examined; 958 cells contained an X chromosome, 1077 a Y chromosome. The ratio of X : Y bearing sperm differed significantly from the expected 1 : 1 ratio (χ2 = 6.96; 0.001 < P < 0.01). Sex-chromosomal hyperhaploidy was detected in 2.67% of the cells (1.22% XX, 1.36% XY, 0.09% YY) and a diploid constitution in 0.23%. Although the frequency of 24,YY sperm was similar to that detected in fertile males, the frequencies of 24,XX, 24,XY and diploid cells were significantly increased. A sex-chromosomal signal was missing in 4.26% of the spermatozoa. This percentage appeared to be too high to be attributed merely to nullisomy for the sex chromosomes and was considered, at least partially, to be the result of superposition of sex-chromosomal hybridization signals by autosomal signals in a number of sperm nuclei. The results contribute additional evidence that 47,XXY cells are able to complete meiosis and produce mature sperm nuclei.

Pregnancy after intracytoplasmic sperm injection with sperm from a man with a 47,XXY Klinefelter's karyotype.

OBJECTIVE To report the initiation of a pregnancy that was achieved by intracytoplasmic sperm injection (ICSI) with sperm from a patient with Klinefelters syndrome. DESIGN Case report. SETTING University womens hospital IVF center. PATIENT(S) A couple with primary infertility and nonmosaic 47,XXY karyotype of the male partner. INTERVENTION(S) Intracytoplasmic sperm injection after ovarian stimulation and transvaginal ultrasound-guided oocyte pick-up with sperm from a hypergonadotropic man with a nonmosaic 47,XXY karyotype. MAIN OUTCOME MEASURE(S) Clinical pregnancy. RESULT(S) Despite a 47,XXY karyotype in all 50 analyzed lymphocyte metaphases, the sperm of the patient led to a clinical pregnancy with the first attempt of ICSI and intrauterine transfer of three embryos. The pregnancy stopped developing in the ninth week. Cytogenetic investigation of the abortion material revealed a numerical normal 46,XXY karyotype. CONCLUSION(S) Sperm from a patient with hypergonadotropic nonmosaic Klinefelters syndrome, when used for ICSI, can lead to a pregnancy.

Recurrent Pregnancy Loss and Its Relation to FV Leiden, FII G20210A and Polymorphisms of Plasminogen Activator and Plasminogen Activator Inhibitor

Thrombophilic disorders and hypofibrinolysis were demonstrated to be risk factors in a majority of women with recurrent pregnancy loss (RPL) and infertility. We investigated the association of FV G1691A mutation, F II G20210A gene polymorphism (PM), 4G/5G PAI-1 and Alu I/D tPA PM in 32 women with infertility and 49 women with at least 2 unexplained early abortions. FV Leiden mutation was significantly more common in women with RPL (10%, p = 0.02) and infertility (19%, p = 0.0005) compared with controls (2%). PAI-1 4G PM and t-PA Alu I PM, alone or in combination, were not associated with RPL or infertility. 9/49 women with RPL showed coagulation disorders with heterozygous FV Leiden mutation (5), FXII (1), protein C (1) or protein S (2) deficiency. However, due to the small number of patients studied, no definite conclusion can be drawn.

Factor XII deficiency is strongly associated with primary recurrent abortions

OBJECTIVE To evaluate factor XII deficiency in women with primary and secondary recurrent abortion. DESIGN Prospective case-control study. SETTING University hospital. PATIENT(S) Sixty-seven women with primary and 33 women with secondary recurrent abortion of unexplained nature and 49 healthy controls with no history of thrombotic disease or adverse pregnancy outcomes. MAIL OUTCOME MEASURE(S): Plasma factor XII activity, activated protein C resistance, factor V Leiden mutation analysis, protein C, protein S, antithrombin III, karyotyping, and anticardiolipin antibodies. RESULT(S) Ten of 67 women with primary recurrent abortion (14.9%) and 4 of 33 women (12.1%) with secondary recurrent abortion had reduced factor XII activity (<60%). These results are highly significant in the former group and showed a tendency toward significance in the latter group. All controls had normal factor XII activity. CONCLUSION(S) Factor XII deficiency is strongly associated with primary recurrent abortion, and women with secondary recurrent abortion show a tendency toward factor XII deficiency.

Factor XII (Hageman) deficiency in women with habitual abortion: new subpopulation of recurrent aborters?

Objective To examine the possible association between factor XII (FXII) deficiency and an elevated number of abortions. Design Factor XII activity, FXII antigen concentration, other blood clotting parameters, and phospholipid antibodies were examined in venous blood from 43 women with repeated (3 to 7) abortions before the 28th week of gestation but without gynecological and chromosomal abnormalities. The data were compared with those obtained from 49 age-matched women without fetal loss. Results Eight cases with moderately reduced FXII activity (35% to 68% of normal) could be identified in the abortion group, whereas among controls no abnormalities in FXII activity and antigen concentration were found. The relative occurrence of reduced FXII level was higher among patients with more than three abortions as compared with those with three abortions. Conclusion Repeated abortions may be associated with reduced level of FXII activity of unknown origin.

Analyzes of three common thrombophilic gene mutations in German women with recurrent abortions

Background.  Several etiological factors have been proposed as a cause for recurrent fetal abortions. Changes in blood coagulation during pregnancy may play an important role in the occurrence of recurrent abortions (RA).

Regulation of Steroid Production and its Function Within the Corpus Luteum

During the second half of the luteal phase, the human corpus luteum becomes responsive to regular luteinizing hormone (LH) pulses. These LH pulses stimulate progesterone secretion tonically, and during this tonic stimulation, additional LH-independent progesterone pulses occur, which are particularly pronounced in women with human chorionic gonadotropin-stimulated luteal function. No progesterone pulses are seen in women suffering from corpus luteum deficiency due to absent LH pulses. The corpus luteum thus has a progesterone pulse generator turned on by gonadotropins but functioning for several hours without further gonadotropic support. This pulse generator appears to be regulated by intraluteal auto-/paracrine mechanisms, which we have investigated in a porcine model using molecular, cellular, and in vivo tools. Luteal oxytocin and progesterone release occurs in tightly coupled pulses. In vivo, oxytocin and prostaglandin F2 alpha(PGF2 alpha) stimulate estradiol and progesterone release and estradiol itself further stimulates progesterone release. Analysis of the different luteal cell compartments (large luteal cells, small luteal cells, fibroblasts) suggests an intraluteal circuit that involves paracrine effects of estradiol, oxytocin, and PGF2 alpha. At the time of luteolysis, the luteotropic effects of estradiol are inhibited by tumor necrosis factor derived from invading macrophages and the intraluteal circuit is thereby disrupted, leading to luteolysis.

Hormonal contraception and depression: a survey of the present state of knowledge

PurposeDepressive symptoms often occur among women of reproductive age. In this article we perform an analysis of existing studies to examine a possible correlation between depression and the use of hormone-based contraceptives.MethodsThe computerized databases MEDLINE/PubMed were searched for studies examining the relation between depressive disorders and hormonal contraception of the years 1976–2010.ResultsData on this topic are limited. At least two confounding variables influence the analysis of the available data and make it difficult to draw firm conclusions: the inconsistent use of the term “depression” and the large number of combined contraceptives which vary in their composition. The association between the use of oral contraceptives and depression is not clear. We found that depression is not a common side effect of hormone-based contraceptives.ConclusionIndividual, patient-based decisions with consideration of the individual history and predispositions are recommended when starting oral contraceptives. If depressive symptoms or mood changes occur, decisions regarding discontinuation or medication change need to be made on an individual basis.

Prognostic value of an automated sperm analysis in IVF or insemination therapy

Summary. During the course of sterility treatment semenograms of 271 IVF and 316 insemination patients were carried out by two automated semen analysers. The parameters of these analyses were correlated to pregnancies resulting from the treatment. Semen samples were analysed in the ejaculate and after swim‐up preparation. In addition, the swim‐up suspension of IVF patients was measured again 18 h after sperm preparation. Patients were divided into three groups: (1) couples who achieved a pregnancy, (2) couples who did not achieve a pregnancy, and (3) IVF patients with no fertilization of the oocytes. Because of large standard deviations in the quality of ejaculates, the results in the IVF group show no significant differences in the semen parameters of husbands of pregnant and non‐pregnant women. In contrast husbands of women with no fertilization have a significantly lower sperm motility. After swim‐up preparation these differences no longer occur. A further measurement, taken 18 h later, reveals that there are no differences in the sperm parameters between the pregnant and non‐pregnant group. However, the semen quality in the group with no fertilization is significantly reduced. The results of the insemination patients are similar to those of the IVF group. Thus, the results from automated sperm analysers cannot replace either the microscopic or biochemical analysis of an ejaculate and, moreover, cannot be used as prognosis for the fertilization capacity of sperms or a following pregnancy.

Homozygous factor V Leiden mutation in a woman with multiple adverse pregnancy outcomes

Abstract We report a case with one intrauterine fetal death (IUFD) at 32 weeks of gestation, one premature delivery at the same week, and one abortion of unknown etiology at 12 weeks of gestation. We discuss that the presence of homozygosity for Factor V Leiden may be associated with placental insufficiency in this woman. Application of anticoagulant therapy may have been beneficial in her current pregnancy.