A 47,XXY fetus conceived after ICSI of spermatozoa from a patient with non-mosaic Klinefelter's syndrome: case report

The birth of 12 healthy infants to fathers with non-mosaic Klinefelter's syndrome has been reported so far. The spermatozoa for these pregnancies was obtained from frozen-thawed ejaculate in one pregnancy (twins) and from the testis in the remaining 10 infants. All of them had a normal karyotype. We describe a patient with non-mosaic Klinefelter's syndrome from whom a testicular biopsy was obtained and motile spermatozoa were collected. Of 16 oocytes that were injected, 14 fertilized and cleaved. Three embryos were transferred, resulting in a triplet pregnancy. Karyotype analysis from chorionic villous sampling revealed 46,XX, 46,XY and 46,XXY from the three fetuses. The affected 46,XXY fetus was reduced on the 14th gestational week. The pregnancy culminated with the birth of a healthy male and female, on the 36th gestational week, weighing 3600 and 2660 g respectively. This case report proves the presence of hyperploid spermatozoa in the seminiferous lumen, and strengthens the necessity of genetic diagnosis of the embryos or fetuses in such pregnancies to fathers with non-mosaic Klinefelter's syndrome.     

Coasting-what is the best formula?

Coasting is a method to decrease the incidence of ovarian hyperstimulation syndrome (OHSS), which involves withdrawing exogenous gonadotrophins until the serum estradiol (E(2)) level decreases. The application of this strategy, as it appears in the literature, has been variable, with heterogeneous criteria for initiating and ending the coasting process and as a result, reports of efficacy are inconsistent. In attempt to establish a recommended protocol for coasting we reviewed and analysed 10 relevant studies, found by a Medline search. Based on the data collected, coasting should be initiated when the serum E(2) concentration exceeds 3000 pg/ml, but not unless the leading follicles reach a diameter of 15-18 mm. Its duration should be limited to <4 days, thus, preventing the decrease in implantation and pregnancy rates that occur after longer periods of coasting. Administration of hCG should be withheld until serum E(2) falls below 3000 pg/ml. Based on the published data, these suggested guidelines result in an acceptably low incidence of severe OHSS (<2%) and provide satisfactory fertilization and pregnancy rates (55-71% and 36.5-63% respectively). A multicentre randomized prospective study would help to confirm the effectiveness of this approach.     

Induction of ovulation after gnRH antagonists

The gonadotrophin-releasing hormone (GnRH) antagonist binds competitively to the receptors and thereby prevents endogenous GnRH from exerting its stimulatory effect on the pituitary cells. This causes suppression of gonadotrophin secretion which occurs immediately after administration of the antagonist. When using GnRH antagonist in controlled ovarian stimulation, ovulation or maturation of the oocyte can, therefore, be induced by a variety of drugs, e.g. native GnRH, recombinant LH or short-acting GnRH agonists. Short-acting GnRH agonists were recommended for triggering ovulation in cases with a high risk of developing ovarian hyperstimulation syndrome (OHSS). Since it is evident that GnRH is required to initiate the LH surge and the oestradiol rise, a single administration of GnRH antagonist during the late follicular phase delays the LH surge. Studies showed that a single s.c. administration of 3 or 5 mg of Cetrorelix in the late follicular stage was sufficient to prevent the LH surge for 617 days. This phenomenon can be used in high responder patients who are prone to OHSS. The question whether this delay has any effect on oocyte quality and maturation still remains unanswered. Overall, there are four uses for GnRH antagonist: (i) using short-acting GnRH agonists for triggering ovulation in cases in which the GnRH antagonist is part of the protocol for ovarian stimulation. Recombinant LH and native LHRH could also be used as triggers of LH surge; (ii) delaying the LH surge in cases prone to OHSS by treatment with GnRH antagonist; (iii) to administer GnRH antagonist during the luteal phase to decrease the activity of corpora lutea; (iv) in polycystic ovarian disease with elevated LH the LH/FSH ratio can be corrected with the injection of GnRH antagonist prior to and during ovarian stimulation.     

Monozygotic twinning after assisted reproductive techniques: a phenomenon independent of micromanipulation

A 3 year retrospective analysis was conducted of pregnancies achieved after various assisted reproductive treatment modalities in our infertility practice, to calculate and compare the rates of monozygotic twinning (MZT). A total of 731 pregnancies achieved after various assisted reproduction treatments were reviewed. Gonadotrophin therapy for induction of ovulation and controlled ovarian hyperstimulation (COH) yielded 129 clinical pregnancies. Conventional IVF yielded 139 pregnancies. IVF and intracytoplasmic sperm injection (ICSI) with or without assisted hatching (AH) yielded 463 pregnancies, all during the same time period. The rates of multiple pregnancy (monozygotic and dizygotic) twins and triplets were recorded. MZT was found in 1.5% of ovulation induction or COH pregnancies (2/129). The incidence of MZT after conventional IVF was 0.72% (1/139). After IVF-ICSI/AH, MZT was found in 0.86% (4/463). The overall rate of MZT was 0.95% (7/731). Five cases were dizygotic triplets and two cases were monozygotic twins. We found the rate of MZT after assisted reproduction treatment increased more than two-fold over the background rate in the general population. Dizygotic triplets were found more often than monozygotic twins. The rate of MZT was consistently increased, irrespective of treatment modality or micromanipulation. This may signify that the aetiology of increased MZT after assisted reproduction is the gonadotrophin treatment rather than in-vitro conditions, micromanipulation, or multiple embryo transfer.     

Intracytoplasmic injection of fresh and cryopreserved testicular spermatozoa in patients with nonobstructive azoospermia—a comparative study

Objective: To compare the outcome of intracytoplasmic sperm injection (ICSI) with fresh and frozen-thawed testicular spermatozoa in patients with nonobstructive azoospermia.Design: Retrospective analysis of consecutive ICSI cycles.Setting: In Vitro Fertilization Unit, Assaf Harofeh Medical Center.Patient(s): Eighteen with nonobstructive azoospermia in whom testicular sperm was found after testicular sperm extraction.Intervention(s): Testicular sperm retrieval, cryopreservation, and ICSI with fresh or frozenthawed testicular spermatozoa.Main Outcome Measure(s): Two-pronuclear fertilization; embryo cleavage rates, mean number of embryos transferred per cycle, and their relative quality, embryo implantation, clinical pregnancy, and ongoing pregnancy rates (PRs) per ET.Result(s): No statistically significant differences were noted in all parameters examined between ICSI cycles with fresh or cryopreserved testicular spermatozoa from the same nine patients and comparing all ICSI cycles performed; with fresh (25 cycles) and thawed (14 cycles) testicular spermatozoa, respectively: two-pronuclear fertilization, 47% versus 44%; embryo cleavage rates, 94% versus 89%; implantation rates, 9% versus 11%; and clinical PR, 26% versus 27%. The delivery or ongoing PR using fresh sperm was better (21% versus 9%), but the difference did not reach statistical significance. The cumulative clinical PRs and ongoing PRs per testicular sperm extraction procedure were 36% and 24%, respectively.Conclusion(s): Testicular sperm cryopreservation using a simple freezing protocol is promising in patients with nonobstructive azoospermia augmenting the overall success achieved after surgical sperm retrieval. (Fertility Sterility 1997;68:892-7. C 1997 by American Society for Reproductive Medicine.)     

Assessment of spatial neglect using computerised feature and conjunction visual search tasks

The purpose of this study was to assess the diagnostic sensitivity of tasks employing feature and conjunction visual searches in stroke patients with unilateral spatial neglect (USN).

Seventy-two stroke patients (right/left hemispheric damage with/without USN) and 39 healthy controls participated in the study. Hit rate and reaction time measures of feature and conjunction searches were tested using a newly developed computerised programme for the assessment of visual spatial attention (VISSTA). In addition, subjects received a set of diagnostic paper-and-pencil tests, and were also assessed for the impact of neglect on activities of daily living. Results indicated that the computerised test clearly differentiated between stroke patients and healthy controls, and between the different patient groups. USN patients showed significant contralesional disadvantage in both feature and conjunction visual search tasks. It is proposed that computerised assessment of visual search capacity is a useful and sensitive adjunct to standard paper-and-pencil tests of USN, with the advantage of testing responses based on attention shifts under a time constraint. The learning effects that limit the usefulness of paper-and-pencil tests in longitudinal studies are less likely to affect a computerised test, making it more suitable for monitoring treatment-induced or natural recovery by way of repeated testing.