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Mitotic errors during early development of human preimplantation embryos are common, rendering a large proportion of embryos chromosomally mosaic. It is also known that the percentage of diploid cells in human diploid-aneuploid mosaic embryos is higher at the blastocyst than at the cleavage stage. In this study, we examined whether there is temporal and/or developmental-stage variation in the occurrence of mitotic errors in human preimplantation embryos from the first day of development onward using mitotically stable digynic tripronuclear human embryos as a model system. All the cells of the 114 digynic tripronuclear human preimplantation embryos included were analyzed by fluorescence in situ hybridization for chromosomes 1, 13, 16, 17, 18, 21, X, and Y. Embryos were grouped according to day of development (1-6) and developmental stage (2-cell to blastocyst stage). The possibility of a mitotic error was highest in the first and second mitotic divisions. The percentage of cells with mitotic errors increased during preimplantation development and was highest at the 9-16 cell stage (76%, P = 0.027). Thereafter, the percentage of cells with mitotic errors decreased to 64% at the morula and 56% at the blastocyst stage. The pattern found correlates with the activation of the embryonic genome at the 8-16 cell stage. A better insight in the timing of occurrence of mitotic errors in human preimplantation embryos could help in understanding and prevention of these errors and is relevant in the context of PGS

Current cancer treatment regimens do not only target tumor cells, but can also have devastating effects on the spermatogonial stem cell pool, resulting in a lack of functional gametes and hence sterility. In adult men, fertility can be preserved prior to cancer treatment by cryopreservation of ejaculated or surgically retrieved spermatozoa, but this is not an option for prepubertal boys since spermatogenesis does not commence until puberty. Cryopreservation of a testicular biopsy taken before initiation of cancer treatment, followed by in vitro propagation of spermatogonial stem cells and subsequent autotransplantation of these stem cells after cancer treatment, has been suggested as a way to preserve and restore fertility in childhood cancer survivors. This strategy, known as spermatogonial stem cell transplantation, has been successful in mice and other model systems, but has not yet been applied in humans. Although recent progress has brought clinical application of spermatogonial stem cell autotransplantation in closer range, there are still a number of important issues to address. In this paper, we describe the state of the art of spermatogonial stem cell transplantation and outline the hurdles that need to be overcome before clinical implementation.

Cryopreservation of spermatozoa and embryos has been a standard procedure in Dutch fertility laboratories for several decades. Until recently, oocyte cryopreservation was rarely performed because of the low chance of survival. 'Vitrification' is a promising new technique for the freezing of oocytes. This ultra-quick freezing method can be used when no spermatozoa, or no viable spermatozoa, could be obtained during in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), and for patients with cancer who have to undergo potentially damaging oncology treatment. The Academic Medical Center in Amsterdam has performed oocyte vitrification for 20 patients in the period March 2006 - October 2009. Ten of these patients have undergone ICSI treatment; this resulted in three pregnancies and the birth of two healthy babies from two of these pregnancies

Marleen Nahuis1,2,3, Fulco van der Veen1, Jur Oosterhuis2, Ben Willem Mol1, Peter Hompes3, Madelon van Wely11Center for Reproductive Medicine, Department of Obstetrics and Gynaecology (H4-205), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; 2Department of Obstetrics and Gynaecology, Medisch Spectrum Twente, Enschede, The Netherlands; 3Department of Obstetrics and Gynaecology, Free Medical University, Amsterdam, The NetherlandsAbstract: Anovulation is a common cause of female subfertility. Treatment of anovulation is aimed at induction of ovulation. In women with clomiphene-citrate resistant WHO group II anovulation, one of the treatment options is ovulation induction with exogenous follicle-stimulating hormone (FSH or follitropin). FSH is derived from urine or is produced as recombinant FSH. Two forms of recombinant FSH are available – follitropin alpha and follitropin beta. To evaluate the efficacy, safety, costs and acceptability of recombinant FSH, we performed a review to compare recombinant FSH with urinary-derived FSH products. Follitropin alpha, beta and urinary FSH products appeared to be equally effective in terms of pregnancy rates. Patient safety was also found to be comparable, as the incidence of side effects including multiple pregnancies was similar for all FSH products. In practice follitropin alpha and beta may be more convenient to use due to the ease of self-administration, but they are also more expensive than the urinary products.Keywords: follitropin apha, follitropin beta, urinary gonadotropins, polycystic ovary syndrome

OBJECTIVE: To assess the predictive capacity of male and female characteristics on in vitro fertilization (IVF) outcome in couples with male subfertility and to construct an IVF prediction model. STUDY DESIGN: We performed a cohort study including all couples with male subfertility undergoing IVF. The main outcome measure was an ongoing pregnancy after IVF. The baseline characteristics from a couple including parameters of the semen-analysis were included in a univariable and multivariable analysis to construct a prediction model (model I). The addition of antisperm antibodies (ASA) and post-wash total motile count (TMC) to models I, II and III, respectively, were analyzed. RESULTS: We included 275 couples with male subfertility who underwent 473 IVF cycles with an ongoing pregnancy rate of 19% per cycle. A prediction model containing female age, secondary subfertility, percentage progressively motile sperm, percentage sperm with normal morphology, prewash total motile sperm count, bilateral tubal pathology, history of intrauterine insemination and cycle number was constructed (model I). Prediction with model I resulted in the selection of 95 couples, of whom 55 conceived (pregnancy rate of 28% per cycle). Use of the model with n ASA (Model II) resulted in the selection of 79 couples, of whom still 55 conceived (30% per cycle). CONCLUSION: In couples with male subfertility, the use of a prediction model including ASA improves the efficiency of IVF

OBJECTIVE: To compare reproductive outcomes in couples carrying a structural chromosome abnormality and non-carrier couples referred for chromosome analysis after two or more miscarriages. DESIGN: Index [corrected]-control study. SETTING: Six centres for clinical genetics in the Netherlands. PARTICIPANTS: 278 carrier couples and 427 non-carrier couples referred for chromosome analysis between 1992 and 2000 after two or more miscarriages before 20 weeks of gestation. Couples were followed up for at least 24 months after chromosome analysis. MAIN OUTCOME MEASURES: The birth of at least one healthy child, at least one more miscarriage, and viable offspring with unbalanced chromosomal abnormalities after parental chromosome analysis. RESULTS: Mean follow-up after chromosome analysis was 5.8 years. 120 of 247 (49%) carrier couples had one or more miscarriage after chromosome analysis compared with 122 of 409 (30%) non-carrier couples (difference 19%, 95% confidence interval 11% to 26%; P < 0.01). The percentage of couples with at least one healthy child was not significantly different in carrier couples (83%) and non-carrier couples (84%) (difference -1%, - 7% to 5%). Among 550 pregnancies in carrier couples, two viable unbalanced chromosome abnormalities were detected at prenatal diagnosis (0.4%) and the fetuses aborted and two children with an unbalanced karyotype were born (0.4%). CONCLUSIONS: Couples whose carrier status was ascertained after two or more miscarriages have a low risk of viable offspring with unbalanced chromosomal abnormalities. Their chances of having a healthy child are as high as non-carrier couples, despite a higher risk of miscarriage

The purpose of our study was to establish the value of a laparoscopic electrocautery strategy compared with ovulation induction with rFSH (recombinant follicle-stimulating hormone) in women with clomiphene citrate (CC) resistant polycystic ovary syndrome (PCOS), with clinical effectiveness, safety, quality of life, expenses and preference of the women as outcome measures. The randomised study took place in 29 Dutch hospitals between February 1998 and October 2001 in 168 women with CC-resistant PCOS. Eighty-three of these women were randomised to an electrocautery strategy consisting of laparoscopic electrocoagulation of the ovaria, followed by CC and rFSH with persistent anovulation and 85 women were randomised to ovulation induction with rFSH. The primary outcome measure of the study was the attainment of an ongoing pregnancy within 12 months. Electrocoagulation strategy and ovulation induction with rFSH were similar with respect to the chance of an on-going pregnancy and the costs for the treatment in 12 months' time. Moreover, there were hardly any differences between the two treatment groups in health-related quality of life and treatment preference. However, the electrocoagulation strategy resulted in significantly fewer multiple pregnancies and should therefore be the treatment of choice.